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Capsaicin-Induced Activation of p53-SMAR1 Auto-Regulatory Loop Down-Regulates VEGF in Non-Small Cell Lung Cancer to Restrain Angiogenesis

Capsaicin-Induced Activation of p53-SMAR1 Auto-Regulatory Loop Down-Regulates VEGF in Non-Small Cell Lung Cancer to Restrain Angiogenesis | A Tale of Two Medicines | Scoop.it

Lung cancer is the leading cause of cancer-related deaths worldwide. Despite decades of research, the treatment options for lung cancer patients remain inadequate, either to offer a cure or even a substantial survival advantage owing to its intrinsic resistance to chemotherapy. Our results propose the effectiveness of capsaicin in down-regulating VEGF expression in non-small cell lung carcinoma (NSCLC) cells in hypoxic environment. Capsaicin-treatment re-activated p53-SMAR1 positive feed-back loop in these cells to persuade p53-mediated HIF-1α degradation and SMAR1-induced repression of Cox-2 expression that restrained HIF-1α nuclear localization. Such signal-modulations consequently down regulated VEGF expression to thwart endothelial cell migration and network formation, pre-requisites of angiogenesis in tumor micro-environment. The above results advocate the candidature of capsaicin in exclusively targeting angiogenesis by down-regulating VEGF in tumor cells to achieve more efficient and cogent therapy of resistant NSCLC.

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A Tale of Two Medicines
Natural Medicine, Pharmaceuticals and GMO’s, the Good, the Bad and the OMG! - (The information provided is not intended to be a substitute for professional medical advice, diagnosis or treatment.  Never disregard professional medical advice, or delay in seeking it, because of something you have read on this scoopit page.)
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Curcumin Attenuates Severity of Premenstrual Syndrome Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial

Curcumin Attenuates Severity of Premenstrual Syndrome Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial | A Tale of Two Medicines | Scoop.it

The baseline level of PMS symptoms of before intervention did not differ between groups. While after three consecutive cycles treatment with Curcumin, total severity of PMS score had reduced from 102.06 ± 39.64 to 42.47 ± 16.37 (mean change: 59.59; 95% confidence interval [CI]: 46.19-72.99) and in Placebo, total severity of PMS score changed from 106.06 ± 44.12 to 91.60 ± 43.56 (mean change: 14.45; 95% CI: 2.69 to 26.22). Furthermore, difference between mean changes was significant (mean difference: 45.14; 95% CI: 6.10—14.98).

 

Our results for the first time showed a potential advantageous effect of curcumin in attenuating severity of PMS symptoms, which were probably mediated by modulation of neurotransmitters and anti-inflammatory effects of curcumin.

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A retrospective study of survival in breast cancer patients undergoing deuterium depletion in addition to conventional therapies

A retrospective study of survival in breast cancer patients undergoing deuterium depletion in addition to conventional therapies | A Tale of Two Medicines | Scoop.it
There is increasing evidence that the heavy isotope of hydrogen, deuterium (D), has a pivotal role in cell signalling and that its depletion through the replacement of normal drinking water with deuterium-depleted water (DDW) results in tumour necrosis. The impact of D–depletion on breast cancer outcome was studied retrospectively. The normal daily water intake (150 ppm D) of 232 breast cancer patients was replaced with DDW (65-105 ppm D) for at least 91 days, without altering conventional treatment regimens. According to staging at initial diagnosis, patients with early stage breast cancer (n=158) achieved a median survival time (MST) of 217 months (18.1 years), compared with 52 months (4.3 years) in patients with advanced disease (n=74). The MST is pending in the subgroup of patients who were in remission at the start of DDW treatment; only one out of 48 patients died during the cumulative follow-up period of 221.1 years. Although single DDW treatment was effective, an outstandingly long MST of 24.4 years was attained in the subgroup of 53 patients who were treated with DDW at least twice. In comparison with published data, DDW treatment in combination with or as an extension of conventional therapies noticeably prolonged MST in certain subgroups of breast cancer patients. D-depletion may also be a highly effective therapy for preventing the recurrence of breast cancer. Furthermore, the method is safe and can be easily integrated into standard treatment regimens for breast cancer.
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New evidence for how green tea and apples could protect health.

New evidence for how green tea and apples could protect health. | A Tale of Two Medicines | Scoop.it

Scientists from the Institute of Food Research have found evidence for a mechanism by which certain food compounds could help protect our health.

 

Dietary studies have shown that people who eat the largest amounts of fruit and vegetables have a reduced risk of developing chronic conditions, such as heart disease and cancer. There could be several reasons for this. Some fruit and vegetables naturally contain high amounts of compounds called polyphenols, which could provide protective health benefits.

 

In this study, Dr Paul Kroon and his team at IFR have shown that polyphenols in green tea and apples block a signalling molecule called VEGF, which in the body can trigger atherosclerosis and is a target for some anti-cancer drugs.

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Methanol extract of the ethnopharmaceutical remedy Smilax spinosa exhibits anti-neoplastic activity

Methanol extract of the ethnopharmaceutical remedy Smilax spinosa exhibits anti-neoplastic activity | A Tale of Two Medicines | Scoop.it
Plants have been the source of several effective drugs for the treatment of cancer and over 60% of anticancer drugs originate from natural sources. Therefore, extracts of the rhizome of Smilax spinosa, an ethnomedicinal plant from Guatemala which is used for the treatment of inflammatory conditions, were investigated regarding their anti-neoplastic activities. By using several solvents the methanol extract was by far the most potent against HL60 cell proliferation (50% inhibition at 60 µg/ml). Furthermore, fractionation of this extract yielded fraction F2, which exhibited enforced pro-apoptotic activity, and activated CYP1A1. Proteins that are relevant for cell cycle progression and apoptosis, as well as proto-oncogenes were investigated by western blotting. This revealed that the methanol extract increased the levels of p21 and this may have caused cell cycle attenuation. The derivative fraction F2 induced apoptosis through the intrinsic pathway, which correlated with the inhibition of Stat3 phosphorylation and concomitant induction of caspase 9, then caspase 8 and caspase 3. In summary, the methanol extract and the derivative fraction F2 of S. spinosa showed anti-neoplastic effects in HL-60 cells and CYP1A1 activation in estrogen receptor-positive MCF-7 breast cancer cells but not in estrogen-negative MDA-MB231 breast cancer cells. Based on our data Smilax spinosa may be a promising source for novel anticancer agents.
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Deuterium Depleted Water Effects on Survival of Lung Cancer Patients and Expression of Kras, Bcl2, and Myc Genes in Mouse Lung

Deuterium Depleted Water Effects on Survival of Lung Cancer Patients and Expression of Kras, Bcl2, and Myc Genes in Mouse Lung | A Tale of Two Medicines | Scoop.it
Although advances in cancer therapies continue to develop, the shortness of the survival of lung cancer patients is still disappointing. Therefore, finding new adjuvant strategies is within the focus of cancer cure. Based on observations that deuterium depletion inhibits the growth of cancer cell lines and suppresses certain proto-oncogenes, we have conducted a clinical study in 129 patients with small cell and nonsmall cell lung cancers who consumed deuterium-depleted drinking water (DDW) as a nontoxic agent in addition to conventional chemotherapy and radiotherapy. Median survival time (MST) was 25.9 mo in males and 74.1 mo in female patients; the difference between genders was statistically significant (p < 0.05). Median survival of subjects with brain metastasis was 27.1 mo. Cumulative 5-yr survival probabilities were 19%, 52%, and 33% in males, females, and all patients with brain metastasis, respectively. Gene expression analysis in mouse lung indicated that DDW attenuates 7,12-dimethylbenz(a)anthracene (DMBA)-induced expression of Bcl2, Kras, and Myc in females. In conclusion, DDW counteracts the DMBA-induced overexpression of Bcl2, Kras and Myc genes in mouse lung, and it may extend survival of lung cancer patients as a nontoxic anticancer dietary supplement, especially for women with tumors overexpressing cancer-related genes, because MST of DDW-consuming group was 2–4 times longer than it is generally observed in lung cancer patients.
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Successful treatment of metastatic malignant melanoma with Viscum album extract (Iscador M).

Successful treatment of metastatic malignant melanoma with Viscum album extract (Iscador M). | A Tale of Two Medicines | Scoop.it

Recent study results demonstrate possible clinical benefit from adjuvant treatment with a standardized mistletoe (Viscum album) extract in patients with malignant melanoma.

 

We present a male patient, currently 68 years of age, with one malignant melanoma at the upper part of the right arm since 1992, and another nodular melanoma at the left shoulder, first diagnosed in 1999. After discovery of the second melanoma and surgical resection, the patient was exclusively treated with standardized mistletoe extract (Iscador, (R)M; Weleda AG, CH-Arlesheim, Switzerland). COURSE OF THERAPY AND RESULTS: In June 1992, histologic analysis confirmed the presence of stage IA superficially spreading malignant melanoma with low infiltration of the papillary dermis in a skin excision sample from the upper part of the right arm. In November 1999, another melanoma was surgically removed at the patient's right shoulder. In this case, the histologic examination revealed nodular melanoma, stage IIA (pT3, pN0, M0). Therapy with mistletoe extract was introduced shortly afterwards as the sole adjuvant treatment. During the course of the mistletoe therapy, axillary removal of 8 lymph nodes became necessary, 3 of which proved to be metastatic. First signs of a defined solitary liver metastasis in an area next to segments IV and V were detected during an abdominal ultrasound examination in September 2001. This finding was confirmed by further sonographic examinations. The solitary liver metastasis was not resected, nor was classical antitumor treatment (chemotherapy or radiotherapy) initiated. The patient continued subcutaneous treatment with Iscador M after dose adaptation to 2 mg twice weekly (0.2 mL of a 10-mg vial); the treatment is still ongoing to the present. By June 2002, complete remission of the liver metastasis was diagnosed by liver ultrasound examination. There has been no local relapse so far, and the patient has been in stable condition ever since. No further metastases were discovered so far (as of May 2006).

 

The use of low-dose Iscador as the sole postoperative modality for the adjuvant treatment of metastatic melanoma was extremely effective and very well tolerated in this patient. It achieved complete response and absence of all complaints.

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Interaction mechanism between green tea extract and human α-amylase for reducing starch digestion

This study evaluated the inhibitory effects of the green tea extract on human pancreatic α-amylase activity and its molecular mechanism. The green tea extract was composed of epicatechin (59.2%), epigallocatechin gallate (14.6%) and epicatechin gallate (26.2%) as determined by HPLC analysis. Enzyme activity measurement showed that % inhibition and IC50 of the green tea extract (10%, based on starch) were 63.5% and 2.07 mg/ml, respectively. The Michaelis–Menten constant remained unchanged but the maximal velocity decreased from 0.43 (control) to 0.07 mg/(ml × min) (4 mg/ml of the green tea extract), indicating that the green tea extract was an effective inhibitor against α-amylase with a non-competitive mode. The fluorescence data revealed that the green tea extract bound with α-amylase to form a new complex with static quenching mechanism. Docking study showed the epicatechin gallate in the green tea extract presented stronger affinity than epigallocatechin gallate, with more number of amino acid residues involved in amylase binding with hydrogen bonds and Van der Waals forces. Thus, the green tea extract could be used to manipulate starch digestion for potential health benefits.
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Scientists unveil map of 'epigenome,' a second genetic code

The epigenome map published on Wednesday shows how each of 127 tissue and cell types differs from every other at the level of DNA. Because scientists involved in the Roadmap project have been depositing their findings in a public database as they went along, other researchers have been analyzing the information before the map was formally published.

 

One of the resulting studies show, for instance, that brain cells from people who died with Alzheimer's disease had epigenetic changes in DNA involved in immune response. Alzheimer's has never been seen as an immune-system disorder, so the discovery opens up another possible avenue to understand and treat it.

 

Other researchers found that because the epigenetic signature of different kinds of cells is unique, they could predict with nearly 90 percent accuracy where metastatic cancer originated, something that is unknown in 2 percent to 5 percent of patients.

 

As a result, epigenetic information might offer a life-saving clue for oncologists trying to determine treatment, said co-senior author Shamil Sunyaev, a research geneticist at Brigham and Women's Hospital in Boston.

 

There is much more to come. Instead of the epigenome map being the end, said Kellis, "I very much see (it) as beginning a decade of epigenomics."

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Epigenetic Drivers of Somatic Mutations in Cancer.

Epigenetic Drivers of Somatic Mutations in Cancer. | A Tale of Two Medicines | Scoop.it

Conventional wisdom has steered scientists for many years toward the assumption that disease-triggering genetic mutations were inherited by offspring from existing mutations within parental DNA, and that these mutations reside within all somatic cells, eventually emerging due to some perturbation of the cellular environment. However, over the past several years experimental and genomic data has shown that many of the mutations that lead to carcinogenesis originate somatically, i.e., de novo  mutations generated in offspring that are undetectable in either parent.

 

While inherited (germline) mutations are ascribable, since they follow familial genetic patterns, the underlying causes and traceability of somatic mutations has been problematic for many years. However, due to the increased accessibility and cost effectiveness of next-generation sequencing (NGS) techniques such as whole- genome sequencing (WGS) and whole-exome sequencing (WES), researchers have been able to readily identify somatic mutations and begin to categorize them based on the nature of the mutation, as well as the tissue from where it was derived.     

 

Reporting in the February issue of Nature for example, scientists at Harvard University and the Broad Institute analyzed 173 cancer genomes from eight different cancer types, which represented a wide array of tissue origins. The researchers compared the distribution of mutations in these cancer genomes to 424 epigenetic markers from similar tissue origins where the cancers were derived. The researchers found that the genomic dispersal of epigenetic features aligned to the tumor’s tissue and cell type origin. This led the authors to conclude that “the DNA sequence of a cancer genome encompasses a wealth of information about the identity and epigenomic features of its cell of origin.”

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Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol

Overcoming the Bell-Shaped Dose-Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol | A Tale of Two Medicines | Scoop.it
Cannabidiol (CBD), a major constituent of Cannabis, has been shown to be a powerful anti-inflammatory and anti-anxiety drug, without exerting a psychotropic effect. However, when given either intraperitoneally or orally as a purified product, a bell-shaped dose-response was observed, which limits its clinical use. In the present study, we have studied in mice the anti-inflammatory and anti-nociceptive activities of standardized plant extracts derived from the Cannabis sativa L., clone 202, which is highly enriched in CBD and hardly contains any psychoactive ingredients. In stark contrast to purified CBD, the clone 202 extract, when given either intraperitoneally or orally, provided a clear correlation between the anti-inflammatory and anti-nociceptive responses and the dose, with increasing responses upon increasing doses, which makes this plant medicine ideal for clinical uses. The clone 202 extract reduced zymosan-induced paw swelling and pain in mice, and prevented TNFα production in vivo. It is likely that other components in the extract synergize with CBD to achieve the desired anti-inflammatory action that may contribute to overcoming the bell-shaped dose-response of purified CBD. We therefore propose that Cannabis clone 202 (Avidekel) extract is superior over CBD for the treatment of inflammatory conditions.
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White tea (Camellia sinensis) inhibits proliferation of the colon cancer cell line, HT-29, activates caspases and protects DNA of normal cells against oxidative damage

The present study demonstrates the antioxidant, anticancer and DNA protective effects of white tea (C.sinensis). White tea extract exhibited a strong antioxidant activity in the five assays carried out, i.e., the FRAP, DPPH, nitric oxide, superoxide anion and hydroxyl radical scavenging assays. The high antioxidant activities correlated significantly to their phenolic content. Pre-treatment of 3T3-L1 cells with the extract protected against H2O2-induced DNA damage.

 

The tea extracts also showed high anti-proliferative activity against HT-29 cells, without being toxic to normal fibroblasts. The extract inhibited HT-29 colon cancer cells by the death receptor and mitochondrial apoptotic pathways as demonstrated by increased expression levels of caspases-3/7, -8 and -9.

 

In conclusion, white tea extracts show potential as chemotherapeutic agents. Regular consumption of white tea could maintain good health and protect the body against disease.

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Steamed ginger (Zingiber officinale): Changed chemical profile and increased anticancer potential

Ginger, from the rhizome of Zingiber officinale Rosco (Zingiberaceae), is a common condiment for foods and beverages. In this work, we tested a hypothesis that a steaming process affects the chemical profile and anticancer potential of ginger. An HPLC method with TOF/MS and DAD was developed to analyse the chemical constituents in ginger. The antiproliferative effect of fresh, dried and steamed gingers was evaluated using human Hela cancer cells. The results showed that the antiproliferative effect of steamed ginger at 120 °C for 4 h was approximately 1.5- and 2-fold higher than that of dried and fresh ginger, respectively. Twenty-two components were characterised in the steamed ginger. The decreased concentration of gingerols and increased levels of shogaols contributed to the improved anticancer potential of the steamed ginger. This study elucidated the relationship of the heating process with the constituents and anticancer activity, and developed an optimised processed ginger extract for chemoprevention.

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Nature’s pharmacy – plant-based active substance kills renal cancer cells

Nature’s pharmacy – plant-based active substance kills renal cancer cells | A Tale of Two Medicines | Scoop.it

Nature holds many compounds in store that are of great value to medical research. Recently, for example, scientists discovered that a substance contained in an African shrub kills cancer cells in the kidney. Together with colleagues from Berlin and Leeds, researchers from the Max Planck Institute of Molecular Physiology in Dortmund discovered that the molecule known as englerin A significantly increases the concentration of calcium in cells, causing the cancer cells to die. Englerin A only activates the calcium channels of renal cancer cells, but not those of healthy cells. In cooperation with the Lead Discovery Center in Dortmund, the scientists now want to find out whether englerin A could potentially be used as an innovative drug to treat renal cancer in the future.

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Deuterium content of water increases depression susceptibility: The potential role of a serotonin-related mechanism

Deuterium content of water increases depression susceptibility: The potential role of a serotonin-related mechanism | A Tale of Two Medicines | Scoop.it
Environmental factors can significantly affect disease prevalence, including neuropsychiatric disorders such as depression. The ratio of deuterium to protium in water shows substantial geographical variation, which could affect disease susceptibility. Thus the link between deuterium content of water and depression was investigated, both epidemiologically, and in a mouse model of chronic mild stress. We performed a correlation analysis between deuterium content of tap water and rates of depression in regions of the USA. Next, we used a 10-day chronic stress paradigm to test whether 2-week deuterium-depleted water treatment (91 ppm) affects depressive-like behavior and hippocampal SERT. The effect of deuterium-depletion on sleep electrophysiology was also evaluated in naïve mice. There was a geographic correlation between a content of deuterium and the prevalence of depression across the USA. In the chronic stress model, depressive-like features were reduced in mice fed with deuterium-depleted water, and SERT expression was decreased in mice treated with deuterium-treated water compared with regular water. Five days of predator stress also suppressed proliferation in the dentate gyrus; this effect was attenuated in mice fed with deuterium-depleted water. Finally, in naïve mice, deuterium-depleted water treatment increased EEG indices of wakefulness, and decreased duration of REM sleep, phenomena that have been shown to result from the administration of selective serotonin reuptake inhibitors (SSRI). Our data suggest that the deuterium content of water may influence the incidence of affective disorder-related pathophysiology and major depression, which might be mediated by the serotoninergic mechanisms.
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Researchers found that: "Substitution of normal drinking water with deuterium-depleted water in mice counteracts the behavioral, transcriptional and proliferative changes typical of the depressive-like state, which was comparable to the effects of the SSRI citalopram. "

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Melanoma Epigenetic Regulators Underlie Melanoma Progression and Therapy-Resistance

Melanoma Epigenetic Regulators Underlie Melanoma Progression and Therapy-Resistance | A Tale of Two Medicines | Scoop.it

In a new study entitled “Decoding the regulatory landscape of melanoma reveals TEADS as regulators of the invasive cell state,” a research team at University of Leuven in Belgium reported two novel master regulators that render melanoma cells capable of invading and metastasizing to different body parts, while promoting their resistance to current clinical therapeutics. The study was published in the journal Nature Communications.

 

Melanoma, the most lethal form of skin cancer, comprises a set of highly heterogeneous subpopulations of cancer cells responsible for its aggressiveness and therapy resistance. Notably, it was previously shown in vitro that each of these subpopulation of cells exhibits different characteristics: while some cells exhibit a proliferative behavior, others already display invasive properties. However, the mechanisms that support melanoma cells’ heterogeneity and differences in phenotype remain largely uncharacterized.

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Inactivation of ATP citrate lyase by Cucurbitacin B: A bioactive compound from cucumber, inhibits prostate cancer growth.

Inactivation of ATP citrate lyase by Cucurbitacin B: A bioactive compound from cucumber, inhibits prostate cancer growth. | A Tale of Two Medicines | Scoop.it
Prostate cancer, a leading cause of cancer-related deaths in males, is well recognized as having late disease on-set (mostly at age 60-70) and showing slow/latent disease development, and strategies to prevent cancer formation in late manhood may have significant health impacts. Cucurbitacin B (CuB) is a naturally occurring compound that is found abundantly in cucumbers and other vegetables, and it is known to exert anti-cancer activities (primarily via apoptosis-induction) in several human cancers. However, its chemopreventive potential for prostate cancer has not yet been investigated. Here, we reported that CuB significantly and specifically inhibited prostate cancer cell growth with low IC50 (~0.3 μM; PC-3 and LNCaP), accompanied by marked apoptosis (Caspase 3/7 activation, PARP cleavage, increase of Annexin V-Alexa Fluor 488 (Alexa488)+ cells and accumulation of Sub-G0/G1 population), whereas normal human prostate epithelial cells (PrEC) were CuB-insensitive. Using a chemopreventive model, pre-treatment of mice with CuB (2 weeks before PC-3 prostate cancer cell implantation) significantly reduced the rate of in vivo tumor-formation. A 79% reduction in tumor size (accompanied by marked in situ apoptosis) was observed in the CuB-treated group (with no noticeable toxicity) vs. controls at day 31. Strikingly, mechanistic investigations demonstrated that CuB drove dose-dependent inhibition of ATP citrate lyase phosphorylation (ACLY; an important enzyme for cancer metabolism) both in vitro and in the CuB-chemopreventive mouse model. Importantly, ACLY over-expression abrogated CuB's apoptotic effects in prostate cancer cells, confirming ACLY as a direct target of CuB. Thus, CuB harbors potent chemopreventive activity for prostate cancer, and we revealed a novel anti-tumor mechanism of CuB via inhibition of ACYL signaling in human cancer.
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Inhibition of pancreatic cancer and potentiation of gemcitabine effects by the extract of Pao Pereira

Inhibition of pancreatic cancer and potentiation of gemcitabine effects by the extract of Pao Pereira | A Tale of Two Medicines | Scoop.it
Lack of effective therapy is a major problem in the treatment of pancreatic cancer. In the present study, we investigated a natural product, the extract of Pao Pereira (Pao), for its anti-pancreatic cancer effect in vitro and in vivo, either alone or in combination with the first-line chemotherapeutic drug gemcitabine (Gem). Pao induced dose-dependent apoptosis to all five tested pancreatic cancer cell lines. The combination of Pao and Gem had a synergistic effect in the inhibition of cell growth, with combination indices (CIs) <1 by Chou-Talalay's median effect analysis based on the isobologram principle. Adding Pao to Gem treatment reduced the concentration of Gem to produce an equitoxic effect on pancreatic cancer cells. In an orthotopic pancreatic xenograft mouse model, mice bearing PACN-1 tumors were treated with Pao and Gem, either alone or in combination. The progression of tumors was monitored longitudinally by imaging of live animals. While Gem did not provide significant inhibition, Pao treatment significantly suppressed tumor growth by 70-72%. Combined Pao and Gem treatment further enhanced the tumor inhibitory effect compared to Gem alone, and markedly reduced metastatic lesions in the peritoneum. Collectively, these data suggest that the extract of Pao possesses anti-pancreatic cancer activity and can enhance the effects of Gem in vitro and in vivo.
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Natural Grape Extracts Regulate Colon Cancer Cells Malignancy

Natural Grape Extracts Regulate Colon Cancer Cells Malignancy | A Tale of Two Medicines | Scoop.it

Natural dietary components are evolutionary-selected molecules able to control inflammation and cancerous transformation and progression. Because many studies assessed the beneficial properties of key molecules extracted from grapes, we aimed at investigating the properties of Liofenol™, a natural red wine lyophilized extract, devoid of alcohol and composed by a miscellaneous of components (polyphenols, flavonoids, anthocyanins). We proved that the colon cancer cell line HCT116 responded to Liofenol™ treatment by reducing their proliferation, in association with an increase of p53 and p21 cell cycle gate keepers. Liofenol™ increased dihydroceramides, sphingolipid mediators involved in cell cycle arrest and reduced proliferation rate. We observed a strong induction of antioxidant response, with the activation of the transcriptional factor Nrf2, involved in redox homeostasis and differentiation, without altering tumor sensitivity to chemotherapy. Liofenol™ induced an important morphology change in HCT116 cells, migration inhibition, undifferentiated stem/stem-like cells markers downregulation, and E-cadherin downregulation, interested in epithelia to mesenchymal malignant transition. We conclude that lyophilized grape extract, at dose comparable to putative dietary doses, can activate molecular pathways, involving Nrf2 signaling and the modulation of structural and signaling sphingolipid mediators that cooperate in promoting differentiation and reducing proliferation of digestive tract cancer cells.

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Caffeine and Caffeic Acid Inhibit Growth and Modify Estrogen Receptor and Insulin-like Growth Factor I Receptor Levels in Human Breast Cancer

Epidemiologic studies indicate that dietary factors, such as coffee, may influence breast cancer and modulate hormone receptor status. The purpose of this translational study was to investigate how coffee may affect breast cancer growth in relation to estrogen receptor-α (ER) status.

 

The influence of coffee consumption on patient and tumor characteristics and disease-free survival was assessed in a population-based cohort of 1,090 patients with invasive primary breast cancer in Sweden. Cellular and molecular effects by the coffee constituents caffeine and caffeic acid were evaluated in ER+ (MCF-7) and ER− (MDA-MB-231) breast cancer cells.

 

Moderate (2–4 cups/day) to high (≥5 cups/day) coffee intake was associated with smaller invasive primary tumors (P trend = 0.013) and lower proportion of ER+ tumors (P trend = 0.018), compared with patients with low consumption (≤1 cup/day). Moderate to high consumption was associated with lower risk for breast cancer events in tamoxifen-treated patients with ER+ tumors (adjusted HR, 0.51; 95% confidence interval, 0.26–0.97). Caffeine and caffeic acid suppressed the growth of ER+ (P ≤ 0.01) and ER− (P ≤ 0.03) cells. Caffeine significantly reduced ER and cyclin D1 abundance in ER+ cells. Caffeine also reduced the insulin-like growth factor-I receptor (IGFIR) and pAkt levels in both ER+ and ER− cells. Together, these effects resulted in impaired cell-cycle progression and enhanced cell death.

 

Conclusion: The clinical and experimental findings demonstrate various anticancer properties of caffeine and caffeic acid against both ER+ and ER− breast cancer that may sensitize tumor cells to tamoxifen and reduce breast cancer growth.

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Potential anti-inflammatory effect of lemon and hot pepper extracts on adjuvant-induced arthritis in mice

Arthritis and related disorders, including rheumatoid arthritis (RA), are common diseases affecting millions of people. The present study aimed to investigate the therapeutic potential of lemon and hot pepper extracts on adjuvant induced arthritis (AIA) in mice. Arthritis was induced by injection of complete Freund adjuvant (CFA) subcutaneously at the planter surface of hind paw, the lemon and hot pepper extracts were administered subcutaneously at the same site twice weekly (100 mg/kg), for 2 weeks starting 2 days after CFA injection. Arthritic scores, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), anti-nuclear antibody (ANA), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and paw histopathology were assessed at the end of the experiment. The extract treatments reduced the severity of arthritic scores in the following order: lemon fruit peel (LFP) > lemon leaf (LL) > hot pepper leaf (HL) during the experimental period as compared with positive control (RA). LFP, LL and HL extracts significantly suppressed ESR, ANA, CRP and TNF-α as compared with RA group. HL, LFP and LL reduced the IL-1β by 63.02%, 47.22%, 44.92%, while IL-6 cytokine production significantly decreased by 29.74%, 28.96%, and 23.93% for IL 6 as compared with RA. Hot pepper fruit (HF) extract treated-group showed a significant decrease for ESR on the other hand there was non-significant difference for TNF-α, IL-6, IL1β, CRP and ANA as compared with RA. Histopathological examination indicated that LFP, LL and HL extracts alleviated infiltration of inflammatory cells and synovial hyperplasia as well as protected joint destruction. The data showed that all extracts except HF have significant anti-arthritic and anti-inflammation effects and suggest that these effects may be mediated via the suppression of pro-inflammatory cytokines.

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Study: Plant-Derived Cannabinoid Extract More Efficacious Than Isolated Compound

Study: Plant-Derived Cannabinoid Extract More Efficacious Than Isolated Compound | A Tale of Two Medicines | Scoop.it

The administration of plant-derived cannabidiol(CBD) extracts provide greater efficacy in the treatment of pain and inflammation than does the use of a purified CBD alternative, according to preclinical datapublished online ahead of print in the journal Pharmacology & Pharmacy.

 

Investigators at the Hebrew University, Institute for Drug Research assessed the anti-inflammatory and anti-nociceptive activities of plant-derived CBD extracts in animals.

 

Researchers reported that extracts derived from a CBD-dominant strain of cannabis provided a wider therapeutic window than did the administration of a purified form of CBD provided by a German pharmaceutical company.

 

Authors concluded that the administration of plant-derived extracts is “superior” to the use of synthetic CBD in the treatment of certain inflammatory diseases.

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Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells.

Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells. | A Tale of Two Medicines | Scoop.it

TRAIL (TNF-related apoptosis inducing ligand) is a promising anti-cancer drug target that selectively induces apoptosis in cancer cells. However, many cancer cells are resistant to TRAIL-induced apoptosis. Therefore, reversing TRAIL resistance is an important step for the development of effective TRAIL-based anti-cancer therapies. We previously reported that knockdown of the TOR signaling pathway regulator-like (TIPRL) protein caused TRAIL-induced apoptosis by activation of the MKK7-c-Jun N-terminal Kinase (JNK) pathway through disruption of the MKK7-TIPRL interaction. Here, we identified Taraxacum officinale F.H. Wigg (TO) as a novel TRAIL sensitizer from a set of 500 natural products using an ELISA system and validated its activity by GST pull-down analysis. Furthermore, combination treatment of Huh7 cells with TRAIL and TO resulted in TRAIL-induced apoptosis mediated through inhibition of the MKK7-TIPRL interaction and subsequent activation of MKK7-JNK phosphorylation. Interestingly, HPLC analysis identified chicoric acid as a major component of the TO extract, and combination treatment with chicoric acid and TRAIL induced TRAIL-induced cell apoptosis via JNK activation due to inhibition of the MKK7-TIPRL interaction. Our results suggest that TO plays an important role in TRAIL-induced apoptosis, and further functional studies are warranted to confirm the importance of TO as a novel TRAIL sensitizer for cancer therapy.

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Berry Extract Boosts Effectiveness of Pancreatic Cancer Therapy.

Berry Extract Boosts Effectiveness of Pancreatic Cancer Therapy. | A Tale of Two Medicines | Scoop.it

A wild berry native to North America may strengthen the effectiveness of a chemotherapy drug commonly used to treat pancreatic cancer, according to new research published in the Journal of Clinical Pathology.

 

A study conducted by researchers at King’s College Hospital and the University of Southampton suggests that adding nutraceuticals to chemotherapy cycles may improve the effectiveness of conventional drugs, particularly in hard to treat cancers, such as pancreatic cancer.


The team tested the effectiveness of extract of chokeberry (Aronia melanocarpa) in killing off cancer cells via apoptosis (programmed cell death) in treated cells.

 

Chokeberry is a wild berry that grows across eastern North America in wetlands and swamp areas. The berry is high in vitamins and antioxidants, including various polyphenols — compounds that are believed to mop up the harmful by-products of normal cell activity.

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Lutein’s role in reducing systemic inflammation revealed

Lutein’s role in reducing systemic inflammation revealed | A Tale of Two Medicines | Scoop.it

Increased intakes of lutein may not only have a direct beneficial role in the macula of the eye, but may also help fight systemic inflammation, according to a new study.

 

Macula is a yellow spot of about five millimeters diameter on the retina. A thin macular pigment can allow the blue light through and destroy the cells. Maintaining high levels of both carotenoids, and therefore the macular pigment, is a valid approach to maintaining eye health and reducing the risk of diseases, like AMD.

 

The new study, published in Acta Ophthalmology , adds to an ever growing body of science supporting the vital role of the carotenoids lutein and zeaxanthin for eye health. These compounds are the only carotenoids capable of filtering the harmful blue light than can damage cells in the eye, the rods and the cones.

 

The researchers recruited 70 people with early stage AMD and randomly assigned to them to receive either 10 mg per day of lutein or placebo for one year.

 

Results  indicated that supplementation with 10 mg per day of lutein  reduced levels of a substance in the body called sC5b-9, a marker of systemic inflammation, compared to placebo.

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The Multifaceted Role of Curcumin in Cancer Prevention and Treatment

The Multifaceted Role of Curcumin in Cancer Prevention  and Treatment | A Tale of Two Medicines | Scoop.it

A plethora of in vitro and in vivo research together with clinical trials conducted over the past few decades substantiate the potential of curcumin as an anti-cancer agent. At the molecular level, curcumin targets numerous pathways, highlighting its ability to inhibit carcinogenesis at multiple levels and thus, potentially circumventing the development of resistance. However, there is a paucity of data to explain the underlying mechanism of its activity. Clinical trials with curcumin indicate safety, tolerability, non-toxicity (even up to doses of 8000 mg/day), and efficacy. These studies provide a solid foundation for more well-controlled studies in larger cohorts as well as open avenues for future drug development. However, curcumin activity is limited by its poor bioavailability and some possible adverse effects. The development of formulations of curcumin in the form of nanoparticles, liposomes, micelles or phospholipid complexes to enhance its bioavailability and efficacy are still in its early stages. Nonetheless, curcumin has established itself as a safe and promising molecule for the prevention and therapy of not only cancer but also other inflammation-driven diseases.

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