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Matti Narkia

Anticancer Properties of Ganoderma Lucidum Methanol Extracts In Vitro and In Vivo - Nut... - 0 views

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    Anticancer properties of Ganoderma lucidum methanol extracts in vitro and in vivo.
    Harhaji Trajković LM, Mijatović SA, Maksimović-Ivanić DD, Stojanović ID, Momcilović MB, Tufegdzić SJ, Maksimović VM, Marjanović ZS, Stosić-Grujicić SD.
    Nutr Cancer. 2009;61(5):696-707.
    PMID: 19838944
    DOI: 10.1080/01635580902898743

    Anticancer activities of various extracts of the medicinal mushroom, Ganoderma lucidum, have been widely demonstrated and are mainly associated with the presence of different bioactive polysaccharides and triterpenoids. We have evaluated and compared in vitro and in vivo the antitumor effects of two preparations from Ganoderma lucidum: a methanol extract containing total terpenoids (GLme) and a purified methanol extract containing mainly acidic terpenoids (GLpme). Both extracts inhibited tumor growth of B16 mouse melanoma cells inoculated subcutaneously into syngeneic C57BL/6 mice and reduced viability of B16 cells in vitro, whereby GLme exhibited stronger effect. Furthermore, anticancer activity of GLme was demonstrated for the first time against two other rodent tumor cell lines, L929-mouse fibrosarcoma and C6-rat astrocytoma. The mechanism of antitumor activity of GLme comprised inhibition of cell proliferation and induction of caspase-dependent apoptotic cell death mediated by upregulated p53 and inhibited Bcl-2 expression. Moreover, the antitumor effect of the GLme was associated with intensified production of reactive oxygen species, whereas their neutralization by the antioxidant, N-acetyl cysteine, resulted in partial recovery of cell viability. Thus, our results suggest that GLme might be a good candidate for treatment of diverse forms of cancers.
Matti Narkia

Glucose restriction can extend normal cell lifespan and impair precancerous cell growth... - 1 views

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    Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression.
    Li Y, Liu L, Tollefsbol TO.
    FASEB J. 2009 Dec 17. [Epub ahead of print]
    PMID: 20019239
    doi: 10.1096/fj.09-149328

    Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells. Moreover, in WI-38/S cells glucose restriction decreased expression of hTERT (human telomerase reverse transcriptase) and increased expression of p16(INK4a). Opposite effects were found in the gene expression of hTERT and p16 in WI-38 cells in response to glucose restriction. The altered gene expression was partly due to glucose restriction-induced DNA methylation changes and chromatin remodeling of the hTERT and p16 promoters in normal and immortalized WI-38 cells. Furthermore, glucose restriction resulted in altered hTERT and p16 expression in response to epigenetic regulators in WI-38 rather than WI-38/S cells, suggesting that energy stress-induced differential epigenetic regulation may lead to different cellular fates in normal and precancerous cells. Collectively, these results provide new insights into the epigenetic mechanisms of a nutrient control strategy that may contribute to cancer therapy as well as antiaging approaches.
Matti Narkia

Induction of Ovarian Cancer Cell Apoptosis by 1,25-Dihydroxyvitamin D3 through the Down... - 0 views

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    Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase.
    Jiang F, Bao J, Li P, Nicosia SV, Bai W.
    J Biol Chem. 2004 Dec 17;279(51):53213-21. Epub 2004 Oct 12.
    PMID: 15485861
    doi: 10.1074/jbc.M410395200

    Overall, the study suggests that the down-regulation of telomerase activity by 1,25(OH)2VD3 and the resulting cell death are important components of the response of OCa cells to 1,25(OH)2VD3-induced growth suppression.

    Progressive shortening of telomere associated with cell divisions limits the life span of normal cells and eventually leads to senescence. To become immortal, human cancers including OCa are invariably associated with activation of mechanism that maintains telomere length. Approximately 85-90% of cancers show reactivation of telomerase. The present study shows that telomerase in OCa cells is down-regulated by 1,25(OH)2VD3. Down-regulation of telomerase is due to decreased stability of hTERT mRNA rather than VDRE-mediated transcriptional repression through the putative VDRE present in the regulatory region of the hTERT gene.

    It is known that the inhibition of telomerase may lead to a phenotypic lag during which cells would continue to divide until the point at which the telomeres became critically short. This phenomenon may explain why the apoptotic induction by 1,25(OH)2VD3 needs the treatment for more than 6 days. As mentioned in the results, no detectable shortening of telomeric repeats was observed in parental OVCAR3 cells after 9 days of treatment with 1,25(OH)2VD3 (Fig. 4D). This is likely due to the fact that the short telomere (about 3 kb) in OVCAR3 cells is very close to the minimal length required for survival and that cells with detectably shorter telomere may have been selected against apoptosis. It has been shown that transformed human cells enter crisis once the terminal restriction fragment of the telomere reaches a length of about 4 kb. This is insufficient to protect chro
Matti Narkia

Mechanisms of Berberine (Natural Yellow 18)-Induced Mitochondrial Dysfunction: Interact... - 0 views

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    Mechanisms of berberine (natural yellow 18)-induced mitochondrial dysfunction: interaction with the adenine nucleotide translocator.
    Pereira CV, Machado NG, Oliveira PJ.
    Toxicol Sci. 2008 Oct;105(2):408-17. Epub 2008 Jul 3.
    PMID: 18599498
    doi: 10.1124/jpet.107.128017

    The data from the present work appear to show that berberine also presents some degree of toxicity to "nontumor" systems, which should be carefully understood. ANT inhibition in nontumor cells by berberine would be responsible for a decrease in energy production and could also result in MPT induction. To the best of our knowledge, no full toxicity assessment exists for berberine in humans, although its use in several commercially available supplements suggests that the compound may present a relatively wide safety interval. In fact, a study with patients with congestive heart failure treated with 1.2 g/day of oral berberine revealed low toxicity and resulted into an average plasma concentration of 0.11 mg/l which would translate into 0.3µM (Zeng and Zeng, 1999Go). Repeated cumulative treatments, alternative forms of formulation (e.g., topical application vs. injection) or more importantly, active mitochondrial accumulation due to its positive charge would be expected to increase its concentration in cells into the range of concentrations used in this study.

    Empirical data from nontraditional medicines plus the use of extensive clinical assays would allow the use of berberine as a promising antimelanoma agent while maintaining its safety for humans. In radial/vertical forms of melanoma, a possible topical application of berberine would also be possible, thus minimizing side effects on other organs.

    In conclusion, the present work identifies the ANT as an important target for berberine, with clear relevance for its proposed antitumor effects.
Matti Narkia

Mitochondrially Targeted Effects of Berberine [Natural Yellow 18, 5,6-dihydro-9,10-dime... - 0 views

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    Mitochondrially targeted effects of berberine [Natural Yellow 18, 5,6-dihydro-9,10-dimethoxybenzo(g)-1,3-benzodioxolo(5,6-a) quinolizinium] on K1735-M2 mouse melanoma cells: comparison with direct effects on isolated mitochondrial fractions.
    Pereira GC, Branco AF, Matos JA, Pereira SL, Parke D, Perkins EL, Serafim TL, Sardão VA, Santos MS, Moreno AJ, Holy J, Oliveira PJ.
    J Pharmacol Exp Ther. 2007 Nov;323(2):636-49. Epub 2007 Aug 17.
    PMID: 17704354
    doi: 10.1124/jpet.107.128017

    The present work shows that berberine is accumulated by mitochondria of a mouse melanoma cell line, leading to mitochondrial fragmentation and dysfunction, accompanied by decreased cellular energy charge. When the effect was compared with the results obtained on isolated mitochondrial fractions, it is observed that regardless of the system used, berberine is toxic for mitochondria. One major limitation of the present study (as in many others) is the lack of knowledge of the real concentration of berberine that reaches mitochondria in intact cells. Although we do not possess data regarding this aspect, it is wise to speculate that mitochondrial berberine concentrations will be much higher than in the bulk cytosol due to electrophoretic accumulation. We believe that the range of berberine concentrations accumulated by mitochondria in intact cells is within the range of concentrations used on isolated mitochondrial fractions in the present study. The present work not only provides insights on the mechanism by which berberine interferes with tumor cell proliferation, demonstrating previously unknown effects on mitochondrial physiology, but also raises a note of caution on the use of berberine as a nontoxic "natural" over-the-counter medication.
Matti Narkia

Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependen... - 0 views

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    Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells.
    Mantena SK, Sharma SD, Katiyar SK.
    Mol Cancer Ther. 2006 Feb;5(2):296-308.
    PMID: 16505103
    doi: 10.1158/1535-7163.MCT-05-0448

    The effectiveness of berberine in checking the growth of androgen-insensitive, as well as androgen-sensitive, prostate cancer cells without affecting the growth of normal prostate epithelial cells indicates that it may be a promising candidate for prostate cancer therapy.

    The evaluation of ancient herbal medicines may indicate novel strategies for the treatment of prostate cancer, which remains the leading cause of cancer-related deaths in American men (1). In our present investigation, we show that a naturally occurring isoquinoline alkaloid, berberine, significantly inhibits the proliferation and reduces the viability of DU145 and PC-3 as well as LNCaP cells (Fig. 1), which suggests that berberine may be an effective chemotherapeutic agent against both androgen-sensitive and androgen-insensitive prostate cancer cells. Importantly, we found that berberine did not exhibit toxicity to nonneoplastic human prostate epithelial cells under the conditions used, except for a moderate reduction in cell viability at higher concentrations when cells were treated in vitro for an extended period of time.

    In conclusion, the results of the present study indicate that berberine inhibits proliferation and induces G1-phase arrest and apoptosis in human prostate cancer cells but not in normal human prostate epithelial cells. In addition, we provide mechanistic evidence that berberine-induced apoptosis in prostate carcinoma cells, particularly hormone-refractory prostate carcinoma cells, is mediated through enhanced expression of Bax, disruption of the mitochondrial membrane potential, and activation of caspase-3.
Matti Narkia

Berberine suppresses in vitro migration and invasion of human SCC-4 tongue sq... - 0 views

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    Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9.
    Ho YT, Yang JS, Li TC, Lin JJ, Lin JG, Lai KC, Ma CY, Wood WG, Chung JG.
    Cancer Lett. 2009 Jul 8;279(2):155-62. Epub 2009 Feb 28.
    PMID: 19251361
    doi:10.1016/j.canlet.2009.01.033

    There is increasing evidence that urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases (MMPs) play an important role in cancer metastasis and angiogenesis. Inhibition of u-PA and MMPs could suppress migration and invasion of cancer cells. Berberine, one of the main constituents of the plant Rhizoma coptidis, is a type of isoquinoline alkaloid, reported to have anti-cancer effects in different human cancer cell lines. There is however, no available information on effects of berberine on migration and invasion of human tongue cancer cells. Here, we report that berberine inhibited migration and invasion of human SCC-4 tongue squamous carcinoma cells. This action was mediated by the p-JNK, p-ERK, p-p38, IκK and NF-κB signaling pathways resulting in inhibition of MMP-2 and -9 in human SCC-4 tongue squamous carcinoma cells. Our Western blowing analysis also showed that berberine inhibited the levels of urokinase-plasminogen activator (u-PA). These results suggest that berberine down-regulates u-PA, MMP-2 and -9 expressions in SCC-4 cells through the FAK, IKK and NF-κB mediated pathways and a novel function of berberine is to inhibit the invasive capacity of malignant cells.
Matti Narkia

Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinom... - 0 views

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    Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase 3 and PARP.
    Mantena SK, Sharma SD, Katiyar SK.
    Carcinogenesis. 2006 Oct;27(10):2018-27. Epub 2006 Apr 18.
    PMID: 16621886
    doi:10.1093/carcin/bgl043

    In the present investigation, we show that berberine, which is present abundantly in Berberis plant species, significantly inhibits the viability, proliferation and induces cell death in human epidermoid carcinoma A431 cells (Figure 1), but this effect was not found in normal human epidermal keratinocytes under the identical conditions, except for a non-significant reduction in cell viability at higher concentrations of berberine (50 and 75 µM) and treatment of cells for a longer period of time (72 h). These data suggested that berberine may be examined as an effective chemotherapeutic agent against non-melanoma skin cancers.

    In conclusion, our study indicates that berberine inhibits growth, induces G1 arrest and apoptotic cell death of human epidermoid carcinoma A431 cells. We also provide mechanistic evidences that berberine-induced apoptosis in human epidermoid carcinoma cells is mediated through disruption of mitochondrial membrane potential and activation of caspase 3 pathway, although other pathways may have a role and that require further investigation. Moreover, further in vivo studies are required to determine whether berberine could be an effective chemotherapeutic agent for the prevention of non-melanoma skin cancers.
Matti Narkia

Systemic Treatment with the Antidiabetic Drug Metformin Selectively Impairs p53-Deficie... - 0 views

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    Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth.
    Buzzai M, Jones RG, Amaravadi RK, Lum JJ, DeBerardinis RJ, Zhao F, Viollet B, Thompson CB.
    Cancer Res. 2007 Jul 15;67(14):6745-52.
    PMID: 17638885
    doi: 10.1158/0008-5472.CAN-06-4447
Matti Narkia

PPARalpha signaling mediates the synergistic cytotoxicity of clioquinol and docosahexae... - 0 views

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    The combination effects index (CI) analysis confirmed the synergy of clioquinol and clofibrate on inhibiting cancer cell viability. Using inhibitors to block PPARalpha signaling diminished the synergistic cytotoxicity of clioquinol and DHA. These results provide pharmacological evidence that the synergistic anticancer action of clioquinol and DHA is mediated by PPARalpha signaling in human cancer cells.

    PPARalpha signaling mediates the synergistic cytotoxicity of clioquinol and docosahexaenoic acid in human cancer cells.
    Tuller ER, Brock AL, Yu H, Lou JR, Benbrook DM, Ding WQ.
    Biochem Pharmacol. 2009 May 1;77(9):1480-6. Epub 2009 Feb 13.
    PMID: 19426685
Matti Narkia

High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks. - Cancer E... - 0 views

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    High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks.
    Kamangar F, Schantz MM, Abnet CC, Fagundes RB, Dawsey SM.
    Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1262-8.
    PMID: 18483349
    doi: 10.1158/1055-9965.EPI-08-0025
Matti Narkia

The beverage maté: a risk factor for cancer of the head and neck. - Head Neck... - 0 views

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    The beverage maté: a risk factor for cancer of the head and neck.
    Goldenberg D, Golz A, Joachims HZ.
    Head Neck. 2003 Jul;25(7):595-601. Review.
    PMID: 12808663
    DOI: 10.1002/hed.10288
Matti Narkia

White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell ... - 0 views

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    White button mushroom phytochemicals inhibit aromatase activity and breast cancer cell proliferation.
    Grube BJ, Eng ET, Kao YC, Kwon A, Chen S.
    J Nutr. 2001 Dec;131(12):3288-93.
    PMID: 11739882
Matti Narkia

Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus)... - 0 views

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    Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus).
    Chen S, Oh SR, Phung S, Hur G, Ye JJ, Kwok SL, Shrode GE, Belury M, Adams LS, Williams D.
    Cancer Res. 2006 Dec 15;66(24):12026-34.
    PMID: 17178902
    doi: 10.1158/0008-5472.CAN-06-2206
Matti Narkia

White button mushroom (Agaricus bisporus) exhibits antiproliferative and proapoptotic p... - 0 views

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    White button mushroom (Agaricus bisporus) exhibits antiproliferative and proapoptotic properties and inhibits prostate tumor growth in athymic mice.
    Adams LS, Phung S, Wu X, Ki L, Chen S.
    Nutr Cancer. 2008;60(6):744-56.
    PMID: 19005974
Matti Narkia

Interleukin 2-mediated conversion of ovarian cancer-associated CD4+ regulatory T cells ... - 0 views

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    Interleukin 2-mediated conversion of ovarian cancer-associated CD4+ regulatory T cells into proinflammatory interleukin 17-producing helper T cells.
    Leveque L, Deknuydt F, Bioley G, Old LJ, Matsuzaki J, Odunsi K, Ayyoub M, Valmori D.
    J Immunother. 2009 Feb-Mar;32(2):101-8.
    PMID: 19238008
    doi: 10.1097/CJI.0b013e318195b59e

    Thus, although the impact of TH17 cells on the evolution of EOC remains to be established, our data suggest that local IL-2 treatment in ovarian cancer may result in the conversion of tumor-associated Treg into TH17 cells, relieve Treg-mediated suppression, and contribute to enhance antitumor immunity.
Matti Narkia

Lysis of tumor cells by natural killer cells in mice is impeded by platelets. - Cancer ... - 0 views

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    Lysis of tumor cells by natural killer cells in mice is impeded by platelets.
    Nieswandt B, Hafner M, Echtenacher B, Männel DN.
    Cancer Res. 1999 Mar 15;59(6):1295-300.
    PMID: 10096562
Matti Narkia

In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membr... - 0 views

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    In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus.
    Cho WC, Leung KN.
    J Ethnopharmacol. 2007 Aug 15;113(1):132-41. Epub 2007 May 31.
    PMID: 17611061
    doi:10.1016/j.jep.2007.05.020    
Matti Narkia

In vitro and in vivo anti-tumor effects of Astragalus membranaceus - Cancer Lett. 2007 ... - 0 views

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    In vitro and in vivo anti-tumor effects of Astragalus membranaceus.
    Cho WC, Leung KN.
    Cancer Lett. 2007 Jul 8;252(1):43-54. Epub 2007 Jan 16.
    PMID: 17223259
    doi:10.1016/j.canlet.2006.12.001
Matti Narkia

Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells - ... - 0 views

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    Ginger inhibits cell growth and modulates angiogenic factors in ovarian cancer cells.
    Rhode J, Fogoros S, Zick S, Wahl H, Griffith KA, Huang J, Liu JR.
    BMC Complement Altern Med. 2007 Dec 20;7:44.
    PMID: 18096028
    doi:10.1186/1472-6882-7-44
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