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Cell Cycle and Cell Division | Learn Science at Nature Education:Scitable

Cell Cycle and Cell Division | Learn Science at Nature Education:Scitable | A Tale of Two Medicines | Scoop.it

The study of the cell cycle focuses on mechanisms that regulate the timing and frequency of DNA duplication and cell division. As a biological concept, the cell cycle is defined as the period between successive divisions of a cell. During this period, the contents of the cell must be accurately replicated. Microscopists had known about cell division for more than one hundred years, but not until the 1950s, through the pioneering work of Alma Howard and Stephen Pelc, did they become aware that DNA replication took place only at a specific phase of the cell cycle and that this phase was clearly separated from mitosis. Howard and Pelc's work in the broad bean, Vicia faba, revealed that the cell goes through many discrete phases before and after cell division. From this understanding, scientists then identified the four characteristic phases of the cell cycle: mitosis (M), gap 1 (G1), DNA synthesis (S), and gap 2 (G2). The study of these phases, the proteins that regulate them, and the complex biochemical interactions that stop or start DNA replication and cell division (cytokinesis) are the primary concerns of cell cycle biologists.

The most significant progress in this research field came with the demonstration that specific protein complexes involving cyclins were critical for regulating the passage of cells through the cell cycle. These early observations came from biological studies of the cells of rapidly dividing fertilized frog eggs as well as mutant yeast cells that could not divide. The observations suggested that regulation of the cell cycle is conserved throughout eukaryotes, which has since proved to be the case. The mechanism of division in bacteria differs from that of eukaryotes, and the control of their cell cycle is also somewhat different, although again it is linked with DNA replication.

 


Via Dr. Stefan Gruenwald
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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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Supplementation of fish oil augments efficacy and attenuates toxicity of 5-fluorouracil in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium-induced colon carcinogenesis.

5-Fluorouracil (5-FU) is used for the treatment of colorectal cancer, but has low therapeutic response rate and severe side effects. Recently, fish oil (FO) rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anticancer drugs. Therefore, the current study is designed to evaluate chemotherapeutic efficacy and toxicity profile of 5-FU in combination with FO in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium (DMH/DSS)-induced colon cancer model.

 

The therapeutic efficacy of 5-FU along with FO was analyzed through assessment of survival rate, tumor burden, volume, serum sialic acid levels, cytokeratin 19 (CK19) expression and index of cell proliferation such as cell cycle progression. Toxicological aspects were evaluated by standard functional and structural parameters related to spleen, gastrointestinal, liver and kidney.

 

In the present study, 5-FU in combination with FO increased the survival rate in carcinogen-treated animals. Synergism of 5-FU and FO was also reflected in significant inhibition in tumor growth and serum sialic acid levels in DMH/DSS model. Moreover, the combination dosage significantly augmented the inhibition of cell cycle progression, as shown by CK19 expression. Additionally, FO ameliorated hematologic depression, gastrointestinal, hepatic and renal toxicity caused by 5-FU as substantiated by a marked improvement in structural and functional alterations of these organs.

 

The supplementation of FO is potentially a promising option for increasing the therapeutic potential and mitigating the side effects of 5-FU.

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Plasma Vitamin D Concentration Influences Survival Outcome After a Diagnosis of Colorectal Cancer

We investigated whether the plasma level of 25-hydroxyvitamin D (25-OHD) after a diagnosis of colorectal cancer (CRC) influences survival outcome.

 

We prospectively studied 1,598 patients with stage I to III CRC. We sought association between plasma 25-OHD and stage-specific survival and tested for interaction between 25-OHD level and variation at the vitamin D receptor (VDR) gene locus. Blood was sampled postoperatively, and plasma was assayed for 25-OHD by liquid chromatography-tandem mass spectrometry. VDR polymorphisms (rs1544410, rs10735810, rs7975232, rs11568820) were genotyped, and haplotypes were inferred by using BEAGLE software. We tested for association between survival and 25-OHD, VDR genotype/haplotype, and after applying a VDR genotype–25-OHD interaction term. We conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to estimate adjusted hazard ratios (HRs).

 

We found strong associations between plasma 25-OHD concentration and CRC-specific (P = .008) and all-cause mortality (P = .003). Adjusted HRs were 0.68 (95% CI, 0.50 to 0.90) and 0.70 (95% CI, 0.55 to 0.89), respectively (highest v lowest 25-OHD tertile), particularly in stage II disease (HR, 0.44; P = .004 for CRC-specific mortality). We detected gene-environment interactions between 25-OHD concentration and rs11568820 genotype for CRC-specific (P = .008) and all-cause (P = .022) mortality, number of protective alleles (P = .004 and P = .018, respectively), and GAGC haplotype at the VDR locus for all-cause mortality (P = .008).

 

In patients with stage I to III CRC, postoperative plasma vitamin D is associated with clinically important differences in survival outcome, higher levels being associated with better outcome. We observed interactions between 25-OHD level and VDR genotype, suggesting a causal relationship between vitamin D and survival. The influence of vitamin D supplementation on CRC outcome will require further investigation.

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microRNAs in Circulation Are Altered in Response to Influenza A Virus Infection in Humans

microRNAs in Circulation Are Altered in Response to Influenza A Virus Infection in Humans | A Tale of Two Medicines | Scoop.it

Changes in microRNA expression have been detected in vitro in influenza infected cells, yet little is known about them in patients. microRNA profiling was performed on whole blood of H1N1 patients to identify signature microRNAs to better understand the gene regulation involved and possibly improve diagnosis. Total RNA extracted from blood samples of influenza infected patients and healthy controls were subjected to microRNA microarray. Expression profiles of circulating microRNAs were altered and distinctly different in influenza patients. Expression of highly dysregulated microRNAs were validated using quantitative PCR. Fourteen highly dysregulated miRNAs, identified from the blood of influenza infected patients, provided a clear distinction between infected and healthy individuals. Of these, expression of miR-1260, -26a, -335*, -576-3p, -628-3p and -664 were consistently dysregulated in both whole blood and H1N1 infected cells. Potential host and viral gene targets were identified and the impact of microRNA dysregulation on the host proteome was studied. Consequences of their altered expression were extrapolated to changes in the host proteome expression. These highly dysregulated microRNAs may have crucial roles in influenza pathogenesis and are potential biomarkers of influenza.

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Fenugreek extract diosgenin and pure diosgenin inhibit the hTERT gene expression in A549 lung cancer cell line.

Fenugreek extract diosgenin and pure diosgenin inhibit the hTERT gene expression in A549 lung cancer cell line. | A Tale of Two Medicines | Scoop.it

rigonella foenum-graecum generally known as fenugreek, has been normally cultivated in Asia and Africa for the edible and medicinal values of its seeds. Fenugreek leaves and seeds have been used widely for therapeutic purposes. Fenugreek seed is recognized to show anti-diabetic and anti-nociceptive properties and other things such as hypocholesterolaemic, and anti-cancer. Diosgenin is a steroidal saponin from therapeutic herbs, fenugreek (T. foenum-graceum L.), has been well-known to have anticancer properties. Telomerase activity is not identified in usual healthy cells, while in carcinogenic cell telomerase expression is reactivated. Therefore telomerase illustrates a promising cancer therapeutic target. We deliberate the inhibitory effect of pure diosgenin and fenugreek extract diosgenin on human telomerase reverse transcriptase gene (hTERT) expression which is critical for telomerase activity. MTT-assay and qRT-PCR analysis were achieved to discover cytotoxicity effects and hTERT gene expression inhibition properties, separately. MTT results exhibited that IC50 for pure diosgenin were 47, 44 and 43 µM and for fenugreek extract diosgenin were 49, 48 and 47 µM for 24, 48 and 72 h after treatment. Culturing cells with pure diosgenin and fenugreek extract diosgenin treatment caused in down regulation of hTERT expression. These results indication that pure and impure diosgenin prevents telomerase activity by down regulation of the hTERT gene expression in A549 lung cancer cell line, with the difference that pure compound is more effective than another.

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Vaccine-Induced Measles Virus-Specific T Cells Do Not Prevent Infection or Disease but Facilitate Subsequent Clearance of Viral RNA

Infection with wild-type measles virus (MeV) induces lifelong protection from reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV) also provides protection from measles. The level of neutralizing antibody is a good indicator of protection, but the independent roles of MeV-specific antibody and T cells have not been identified. In this study, macaques immunized with LAV through a nebulizer and a mouthpiece developed MeV-specific T-cell responses but not neutralizing antibodies. Upon challenge with wild-type MeV, these animals developed rashes and viremias similar to those in naive animals but cleared viral RNA from blood 25 to 40 days faster. The nebulizer-immunized animals also had more robust MeV-specific CD4+ and CD8+ T-cell responses than the naive animals after challenge, characterized by a higher number and better durability of gamma interferon (IFN-γ)-producing cells. Induction of MeV-specific circulating CD4+ and CD8+ T cells capable of producing multiple cytokines correlated with clearance of viral RNA in the nebulizer-immunized macaques. These studies demonstrated that MeV-specific T-cell immunity alone did not prevent measles, but T-cell priming enhanced the magnitude, durability, and polyfunctionality of MeV-specific T cells after challenge infection and correlated with more rapid clearance of MeV RNA.

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Anti-cancer effects of blue-green alga Spirulina platensis, a natural source of bilirubin-like tetrapyrrolic compounds.

Spirulina platensis is a blue-green alga used as a dietary supplement because of its hypocholesterolemic properties. Among other bioactive substances, it is also rich in tetrapyrrolic compounds closely related to bilirubin molecule, a potent antioxidant and anti-proliferative agent. The aim of our study was to evaluate possible anticancer effects of S. platensis and S. platensis-derived tetrapyrroles using an experimental model of pancreatic cancer. The anti-proliferative effects of S. platensis and its tetrapyrrolic components [phycocyanobilin (PCB) and chlorophyllin, a surrogate molecule for chlorophyll A] were tested on several human pancreatic cancer cell lines and xenotransplanted nude mice. The effects of experimental therapeutics on mitochondrial reactive oxygen species (ROS) production and glutathione redox status were also evaluated. Compared to untreated cells, experimental therapeutics significantly decreased proliferation of human pancreatic cancer cell lines in vitro in a dose-dependent manner (from 0.16 g•L-1 [S. platensis], 60 μM [PCB], and 125 μM [chlorophyllin], p<0.05). The anti-proliferative effects of S. platensis were also shown in vivo, where inhibition of pancreatic cancer growth was evidenced since the third day of treatment (p < 0.05). All tested compounds decreased generation of mitochondrial ROS and glutathione redox status (p = 0.0006; 0.016; and 0.006 for S. platensis, PCB, and chlorophyllin, respectively). In conclusion, S. platensis and its tetrapyrrolic components substantially decreased the proliferation of experimental pancreatic cancer. These data support a chemopreventive role of this edible alga. Furthermore, it seems that dietary supplementation with this alga might enhance systemic pool of tetrapyrroles, known to be higher in subjects with Gilbert syndrome.

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Full study: http://www.annalsofhepatology.com/revista/numeros/2014/15_142_v13n2_2014_AnticancerEffects.pdf

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Evaluation of the Effect of Blackcurrant Products on Gut Microbiota and on Markers of Risk for Colon Cancer in Humans.

Evaluation of the Effect of Blackcurrant Products on Gut Microbiota and on Markers of Risk for Colon Cancer in Humans. | A Tale of Two Medicines | Scoop.it

The purpose of this study was to determine in healthy humans whether First Leaf (FL; composed of blackcurrant extract powder, lactoferrin and lutein) and Cassis Anthomix 30 (CAM30; blackcurrant extract powder) can positively modify the colonic microbiota by enhancing the growth of the beneficial bacteria and inactivating the toxic bacterial enzymes which are known to be involved in colonic carcinogenesis. Thirty healthy adult male and female volunteers were recruited for this study. Fluorescent in situ hybridization was carried out to analyse the populations of fecal microbiota. Consumption of FL and CAM30 led to significant increases (P < 0.0001) in the population sizes of lactobacilli and bifidobacteria whereas the population sizes of Clostridium spp. and Bacteroides spp were decreased significantly (P < 0.0001). In addition, feeding of FL and CAM30 decreases the activity of β-glucuronidase (bacterial enzyme which is considered to be one of the enzymes that increases risk for colorectal cancer) and significantly decreased (P < 0.05) the fecal pH. In conclusion, the results of this study open up the possibility that consumption of FL and CAM30 can offer various benefits to human health through acting as novel prebiotic agents via increasing the numbers of beneficial bacteria (lactobacilli and bifidobacteria) in the gut.

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Luteolin Induces Carcinoma Cell Apoptosis through Binding Hsp90 to Suppress Constitutive Activation of STAT3

Luteolin Induces Carcinoma Cell Apoptosis through Binding Hsp90 to Suppress Constitutive Activation of STAT3 | A Tale of Two Medicines | Scoop.it

Abnormal activity of STAT3 is associated with a number of human malignancies. Hsp90 plays a central role in stabilizing newly synthesized proteins and participates in maintaining the functional competency of a number of signaling transducers involved in cell growth, survival and oncogenesis, such as STAT3. Hsp90 interacts with STAT3 and stabilizes Tyr-phosphorylated STAT3. It has been reported that luteolin possesses anticancer activity through degradation of Tyr705-phosphorylated STAT3.

 

We found that overexpression of Hsp90 inhibited luteolin-induced degradation of Tyr705-phosphorylated STAT3 and luteolin also reduced the levels of some other Hsp90 interacting proteins. Results from co-immunoprecipitation and immunoblot analysis demonstrated that luteolin prevented the association between Hsp90 and STAT3 and induced both Tyr705- and Ser727-phosphorylated STAT3 degradation through proteasome-dependent pathway. The molecular modeling analysis with CHARMm–Discovery Studio 2.1(DS 2.1) indicated that luteolin could bind to the ATP-binding pocket of Hsp90. SPR technology-based binding assay confirmed the association between luteolin and Hsp90. ATP-sepharose binding assay displayed that luteolin inhibited Hsp90-ATP binding.

 

Luteolin promoted the degradation of Tyr705- and Ser727-phosphorylated STAT3 through interacting with Hsp90 and induced apoptosis of cancer cells. This study indicated that luteolin may act as a potent HSP90 inhibitor in antitumor strategies.

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Changes in the Contents of Anthocyanins and Other Compounds in Blackberry Fruits Due to Freezing and Long-Term Frozen Storage.

Changes in the Contents of Anthocyanins and Other Compounds in Blackberry Fruits Due to Freezing and Long-Term Frozen Storage. | A Tale of Two Medicines | Scoop.it

The aim of this study was to evaluate the effect of fast and slow freezing and frozen storage on the metabolite content of six blackberry cultivars. The content of metabolites determined with HPLC RI/PDA-MS in stored blackberries was compared with the initial content of the fruit. During frozen storage of fruits a loss of vitamin C up to 80% has been recorded along with changes of color values, which shifted to blue and yellow hues. The color changes were accompanied with increased pH levels and content of anthocyanins. Most of the phenolic groups, sugars, and organic acids showed a better extraction after storage, especially in the slow freezing treatment due to a higher degree of tissue damage by freezing. The ‘Thornless Evergreen’ cultivar was especially rich in sugars, vitamin C, and phenolic compounds, but the highest levels of anthocyanins were determined in ‘Loch Ness’ cultivar.

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Bisphenol-A-induced inactivation of the p53 axis underlying deregulation of proliferation kinetics, and cell death in non-malignant human breast epithelial cells

Bisphenol-A-induced inactivation of the p53 axis underlying deregulation of proliferation kinetics, and cell death in non-malignant human breast epithelial cells | A Tale of Two Medicines | Scoop.it

Widespread distribution of bisphenol-A (BPA) complicates epidemiological studies of possible carcinogenic effects on the breast because there are few unexposed controls. To address this challenge, we previously developed non-cancerous human high-risk donor breast epithelial cell (HRBEC) cultures, wherein BPA exposure could be controlled experimentally. BPA consistently induced activation of the mammalian target of rapamycin (mTOR) pathway—accompanied by dose-dependent evasion of apoptosis and increased proliferation—in HRBECs from multiple donors. Here, we demonstrate key molecular changes underlying BPA-induced cellular reprogramming. In 3/3 BPA-exposed HRBEC cell lines, and in T47D breast cancer cells, proapoptotic negative regulators of the cell cycle (p53, p21WAF1 and BAX) were markedly reduced, with concomitant increases in proliferation-initiating gene products (proliferating cell nuclear antigen, cyclins, CDKs and phosphorylated pRb). However, simultaneous exposure to BPA and the polyphenol, curcumin, partially or fully reduced the spectrum of effects associated with BPA alone, including mTOR pathway proteins (AKT1, RPS6, pRPS6 and 4EBP1). BPA exposure induced an increase in the ERα (Estrogen Receptor): ERβ ratio—an effect also reversed by curcumin (analysis of variance, P < 0.02 for all test proteins). At the functional level, concurrent curcumin exposure reduced BPA-induced apoptosis evasion and rapid growth kinetics in all cell lines to varying degrees. Moreover, BPA extended the proliferation potential of 6/6 primary finite-life HRBEC cultures—another effect reduced by curcumin. Even after removal of BPA, 1/6 samples maintained continuous growth—a hallmark of cancer. We show that BPA exposure induces aberrant expression of multiple checkpoints that regulate cell survival, proliferation and apoptosis and that such changes can be effectively ameliorated.

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Evaluation of the Effect of Blackcurrant Products on Gut Microbiota and on Markers of Risk for Colon Cancer in Humans.

Evaluation of the Effect of Blackcurrant Products on Gut Microbiota and on Markers of Risk for Colon Cancer in Humans. | A Tale of Two Medicines | Scoop.it

The purpose of this study was to determine in healthy humans whether First Leaf (FL; composed of blackcurrant extract powder, lactoferrin and lutein) and Cassis Anthomix 30 (CAM30; blackcurrant extract powder) can positively modify the colonic microbiota by enhancing the growth of the beneficial bacteria and inactivating the toxic bacterial enzymes which are known to be involved in colonic carcinogenesis. Thirty healthy adult male and female volunteers were recruited for this study. Fluorescent in situ hybridization was carried out to analyse the populations of fecal microbiota. Consumption of FL and CAM30 led to significant increases (P < 0.0001) in the population sizes of lactobacilli and bifidobacteria whereas the population sizes of Clostridium spp. and Bacteroides spp were decreased significantly (P < 0.0001). In addition, feeding of FL and CAM30 decreases the activity of β-glucuronidase (bacterial enzyme which is considered to be one of the enzymes that increases risk for colorectal cancer) and significantly decreased (P < 0.05) the fecal pH. In conclusion, the results of this study open up the possibility that consumption of FL and CAM30 can offer various benefits to human health through acting as novel prebiotic agents via increasing the numbers of beneficial bacteria (lactobacilli and bifidobacteria) in the gut.

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Public Library Initiative by PLS and ProQuest | Access to Research

Public Library Initiative by PLS and ProQuest | Access to Research | A Tale of Two Medicines | Scoop.it

From January 2014, over 1.5 million academic articles are available,
free of charge, in participating public libraries across the UK.

Students, independent researchers and small businesses can now access many of the world’s best academic papers through their local libraries, a result of a unique collaboration between librarians and publishers, who have made their journal content available for free.

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Methanolic Extracts of Bitter Melon Inhibit Colon Cancer Stem Cells by Affecting Energy Homeostasis and Autophagy

Bitter melon fruit is recommended in ancient Indian and Chinese medicine for prevention/treatment of diabetes. However its effects on cancer progression are not well understood. Here, we have determined the efficacy of methanolic extracts of bitter melon on colon cancer stem and progenitor cells. Both, whole fruit (BMW) and skin (BMSk) extracts showed significant inhibition of cell proliferation and colony formation, with BMW showing greater efficacy. In addition, the cells were arrested at the S phase of cell cycle. Moreover, BMW induced the cleavage of LC3B but not caspase 3/7, suggesting that the cells were undergoing autophagy and not apoptosis. Further confirmation of autophagy was obtained when western blots showed reduced Bcl-2 and increased Beclin-1, Atg 7 and 12 upon BMW treatment. BMW reduced cellular ATP levels coupled with activation of AMP activated protein kinase; on the other hand, exogenous additions of ATP lead to revival of cell proliferation. Finally, BMW treatment results in a dose-dependent reduction in the number and size of colonospheres. The extracts also decreased the expression of DCLK1 and Lgr5, markers of quiescent, and activated stem cells. Taken together, these results suggest that the extracts of bitter melon can be an effective preventive/therapeutic agent for colon cancer.

 

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The data presented in this paper demonstrates that the methanolic extract of bitter melon is potent in inhibiting the growth of colon cancer cells in Vitro

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Now we know why drugs don't work on pancreatic cancer

Now we know why drugs don't work on pancreatic cancer | A Tale of Two Medicines | Scoop.it

The trouble with treating cancer is that each type has its own quirks. The quirks of pancreatic cancer make it one of the most lethal. The survival period after diagnosis is only four to six months. The main reason is that treatment with drugs – chemotherapy – which has had some success in extending lives for patients with other cancers, fails in the case of pancreatic cancer.

 

The widely believed reason for this failure has been that in pancreatic cancer, the tissue that surrounds the tumour, called the stroma, blocks the delivery of chemotherapy drugs to the tumour. A new study, published in Cancer Cell, questions that logic. It shows that the stroma, instead of supporting tumour progression, inhibits it by activating body’s immune system’s attack on the tumour.

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Powerful Protection Against Cellular Aging.

Powerful Protection Against Cellular Aging. | A Tale of Two Medicines | Scoop.it

Conclusive evidence now indicates that PQQ (pyrroloquinoline quinone) activates cell signaling pathways that have the potential to reverse cellular aging!

 

PQQ has previously been shown to promote growth of new mitochondria within aging cells, up-regulate cellular metabolism, protect neurons, and repair DNA!    

   

These and other synergistic signaling effects have the combined ability to promote longevity at the critical subcellular level.

PQQ has been found in all plant species ever tested. Scientists have gone so far as to state that PQQ may be "vital to life.

 

Scientists have found that PQQ, a critical coenzyme, plays a leading role in boosting critical cell signaling mechanisms.


These signaling pathways regulate a variety of physiological and molecular processes throughout the body processes that have an impact on key biomarkers of aging, such as mitochondrial function   and cellular defense against oxidative stress.

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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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Upregulation of COX-2 in the lung cancer promotes overexpression of multidrug resistance protein 4 (MRP4) via PGE2-dependent pathway

It is apparent that lung cancer is associated with inflammation, with accompanying hallmark elevations of cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) levels. However, the effects of these changes on MRP efflux transporters have not been thoroughly investigated before. Here, we report that upregulation of COX-2 can induce overexpression of MRP4 in both A549 non-small-cell lung cancer cell lines and mouse lung cancer models. In A549 cells, phorbol 12-myristate 13-acetate (PMA) treatment induced upregulation of COX-2 and MRP4 together, but not other MRP transporters. Transient overexpression of human COX-2 cDNA also specifically increased COX-2 and MRP4. Moreover, COX inhibitor treatment and COX-2-specific siRNA significantly inhibited the upregulation of MRP4. Additionally, PMA-treatment increased extracellular PGE2 levels, likely due to increased MRP4 function. Likewise, COX-2-specific siRNA reduced extracellular PGE2 levels. Furthermore, COX-2 upregulation resulted in an increase in mPGES-1, an enzyme responsible for PGE2 production. Finally, metastasized lung cancer model mice exhibited increased expression levels of COX-2 and MRP4, as well as mPGES-1. In conclusion, the present study suggests that overexpression of MRP4 in lung cancer may be attributable to COX-2 upregulation via a PGE2-dependent pathway.

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Anticancer activity of Phyllanthus emblica Linn. (Indian gooseberry): inhibition of transcription factor AP-1 and HPV gene expression in cervical cancer cells.

Plant products of Phyllanthus emblica Linn. are traditionally consumed for its immense nutritive and medicinal values. However, the molecular mechanism(s) by which it exerts it effects is less understood. In this study, we investigated mechanism of action of P. emblica fruit extract (PE) by studying its effect on activator protein-1 (AP-1) activity and human papillomavirus (HPV) transcription that are essential for tumorigenicity of cervical cancer cells. PE resulted in a dose-and time-dependent inhibition of DNA binding activity of constitutively active AP-1 in both HPV16-positive (SiHa) and HPV18-positive (HeLa) cervical cancer cells. PE-induced AP-1 inhibition was found mediated through downregulation of constituent AP-1 proteins, c-Jun, JunB, JunD, and c-Fos; however, the kinetics of their inhibition varied in both the cell types. Inhibition of AP-1 by PE was accompanied by suppression of viral transcription that resulted in growth inhibition of cervical cancer cells. Growth inhibitory activity of PE was primarily manifested through induction of apoptotic cell death. These results suggest that P. emblica exhibits its anticancer activities through inhibition of AP-1 and targets transcription of viral oncogenes responsible for development and progression of cervical cancer thus indicating its possible utility for treatment of HPV-induced cervical cancers.

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Detoxication of Airborne Pollutants by Broccoli Sprout Beverage.

Detoxication of Airborne Pollutants by Broccoli Sprout Beverage. | A Tale of Two Medicines | Scoop.it

This week in the journal Cancer Prevention Research, scientists from Johns Hopkins and China's Qidong Liver Cancer Institute report that daily consumption of a half-cup of "broccoli-sprout beverage"—a tea made with broccoli sprouts—produced rapid, sustained, high-level excretion of benzene in research subjects' urine. Their conclusion, building on prior research, is that broccoli helps the human body break down benzene and excrete its byproducts. As benzene is a known human carcinogen commonly found in polluted air in both urban and rural areas, voiding it is an unmitigated virtue.

 

The broccoli-sprout beverage also increased the levels of the lung irritant acrolein, another common air pollutant, in the subjects' urine. 

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Pumpkin Seed Oil Found to Help Reverse Balding

Pumpkin Seed Oil Found to Help Reverse Balding | A Tale of Two Medicines | Scoop.it

 

Researchers from the Republic of Korea's Pusan National University have confirmed that pumpkin seed oil increases hair growth among balding men.

 

The medical researchers tested the pumpkin seed oil on 76 male patients with moderate androgenic alopecia – male pattern hair loss. None of the patients had tried any previous medication, supplement or topical therapy for at least three months prior to the beginning of the study. The researchers recruited 90 patients, but excluded those with high liver enzyme levels.

 

The patients were divided into two groups and half were given a placebo. The treatment consisted of giving the patients 400 milligrams of the pumpkin seed oil per day in capsules. They were given two capsules before breakfast and two capsules before dinner.

 

After three months and at the end of the study at six months the patients were assessed using blinded practitioner analysis, and given a point score, which ranged from -3 (greatly decreased) to +3 (greatly increased).

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Vitamin K2 and Bone Quality.

Vitamin K is a cofactor required for post-translational gamma-carboxylation of vitamin K-dependent proteins, including coagulation and anti-coagulation factors; osteocalcin (OC), essential for bone metabolism; and matrix Gla proteins (MGP), an inhibitor of artery calcification. In addition to activation of OC, vitamin K 2 induces collagen accumulation in the bone matrix. The principle effects of vitamin K on bone health are not to increase bone mineral density but to promote bone quality and bone strength. Vitamin K 2 , as menaquinone-7 (MK-7), is the only major vitamin K homolog which can activate OC at nutritional doses. The higher efficacy of MK-7 is due to its better bioavailability and longer half-life compared to other vitamin K homologs. Furthermore, a normal nutritional intake of MK-7 has been shown to activate MGP, which inhibit artery calcification, and has been associated with prevention of cardiovascular diseases. Thus, MK-7 is thought to contribute to calcium homeostasis in arteries as well as bones.
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Peaches inhibit breast cancer metastasis in mice

Peaches inhibit breast cancer metastasis in mice | A Tale of Two Medicines | Scoop.it

 

Lab tests at Texas A&M AgriLife Research have shown that treatments with peach extract inhibit breast cancer metastasis in mice.

 

AgriLife Research scientists say that the mixture of phenolic compounds present in the peach extract are responsible for the inhibition of metastasis, according to the study, which was this month published in the Journal of Nutritional Biochemistry.

 

"Cancer cells were implanted under the skin of mice with an aggressive type of breast cancer cells, the MDA-MB-435, and what we saw was an inhibition of a marker gene in the lungs after a few weeks indicating an inhibition of metastasis when the mice were consuming the peach extract," said Dr. Luis Cisneros-Zevallos, a food scientist for AgriLife Research in College Station. "Furthermore, after determining the dose necessary to see the effects in mice, it was calculated that for humans it would be equivalent to consuming two to three peaches per day."

 

This is very important because it can be translated into something that is also beneficial for people, he added.

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Smokers with BRCA2 gene mutation 'have increased lung cancer risk'

Smokers with BRCA2 gene mutation 'have increased lung cancer risk' | A Tale of Two Medicines | Scoop.it

It is well known that mutations in the BRCA genes increase the risk of female breast and ovarian cancers. But for the first time, researchers from The Institute of Cancer Research in the UK have discovered a link between smokers with a BRCA2 gene mutation and increased risk of lung cancer.


According to the American Cancer Society, approximately 224,201 Americans will receive a lung cancer diagnosis this year.

It is common knowledge that smoking is the leading risk factor for lung cancer, causing at least 80% of deaths from the disease.

 

But the researchers of this latest study, led by Richard Houlston, professor of molecular population and genetics at The Institute of Cancer Research (ICR), say past studies have indicated that genetic factors may also increase lung cancer risk.

 

To investigate further, the research team compared the DNA of 11,348 European individuals who had lung cancer with the DNA of 15,861 Europeans who were free of the disease.

 

Their findings, recently published in the journal Nature Genetics, revealed that smokers who had mutations in the BRCA2 gene had a 25% chance of developing lung cancer during their lifetime. Smokers in general have around a 13-15% chance of lung cancer, so the study results show that a BRCA2 gene mutation can increase lung cancer risk even further.

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Epigenetic reactivation of estrogen receptor-α (ERα) by genistein enhances hormonal therapy sensitivity in ERα-negative breast cancer

Epigenetic reactivation of estrogen receptor-α (ERα) by genistein enhances hormonal therapy sensitivity in ERα-negative breast cancer | A Tale of Two Medicines | Scoop.it

Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and normally does not respond to conventional estrogen target-directed therapies. The soybean isoflavone, genistein (GE), has been shown to prevent and inhibit breast cancer and recent studies have suggested that GE can enhance the anticancer capacity of an estrogen antagonist, tamoxifen (TAM), especially in ERα-positive breast cancer cells. However, the role of GE in ERα-negative breast cancer remains unknown.

 

We have evaluated the in vitro and in vivo epigenetic effects of GE on ERα reactivation by using MTT assay, real-time reverse transcription-polymerase chain reaction (RT-PCR) assay, western-blot assay, immunoprecipitation (ChIP) assay, immunohistochemistry and epigenetic enzymatic activity analysis. Preclinical mouse models including xenograft and spontaneous breast cancer mouse models were used to test the efficacy of GE in vivo.

 

We found that GE can reactivate ERα expression and this effect was synergistically enhanced when combined with a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA), in ERα-negative MDA-MB-231 breast cancer cells. GE treatment also re-sensitized ERα-dependent cellular responses to activator 17β-estradiol (E2) and antagonist TAM. Further studies revealed that GE can lead to remodeling of the chromatin structure in the ERα promoter thereby contributing to ERα reactivation. Consistently, dietary GE significantly prevented cancer development and reduced the growth of ERα-negative mouse breast tumors. Dietary GE further enhanced TAM-induced anti-cancer efficacy due at least in part to epigenetic ERα reactivation.

 

Our studies suggest that soybean genistein can epigenetically restore ERα expression, which in turn increases TAM-dependent anti-estrogen therapeutic sensitivity in vitro and in vivo. The results from our studies reveal a novel therapeutic combination approach using bioactive soybean product and anti-hormone therapy in refractory ERα-negative breast cancer which will provide more effective options in breast cancer therapy.

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Antiparasitic effects of Zingiber officinale (Ginger) extract against Toxoplasma gondii.

Antiparasitic effects of Zingiber officinale (Ginger) extract against Toxoplasma gondii. | A Tale of Two Medicines | Scoop.it

Zingiber officinale Roscoe, Ginger, has been used in folk medicine as a medicinal plant, as well as a spice and food in many countries. This research was carried out to evaluate the antiparasitic effect of ginger root extract (GE) and GE/F1 (fraction 1 obtained from GE) against Toxoplasma gondii (T. gondii) in vitro and invivo. The effects of GE and GE/F1 against the proliferation of T. gondii-infected C6 cells and T. gondii were evaluated by several indicators such as an MTT assay, nuclear staining, immunofluorescence staining, apoptotic proteins and animal testing. GE/F1 strongly inhibited the proliferation of T. gondii-infected C6 cells and T. gondii in a dose-dependent manner compared with sulfadiazine. After T. gondii invasion, C6 cells induced the activation of caspase-3, bax, p53 and p21 related to programmed cell death, and GE/F1 effectively suppressed the expression of caspase-3, bax, p53 and p21 causing cell death of the infected host cells. In addition, INF-γ, and IL-8 levels, and the viability of T. gondii-infected mice treated with GE/F1 (500 μg/ml) were not changed or increased during the period of the experiment. These results demonstrate that GE/F1 not only induces anti-T. gondii effects causing the inactivation of apoptotic proteins in infected host cells through the direct inhibition of T. gondii but also has antiparasitic properties which inhibit inflammatory cytokine secretion in vivo.

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