Triterpenes from Ganoderma Lucidum induce autophagy in colon cancer through the inhibition of p38 mitogen-activated kinase (p38 MAPK).
ABSTRACT Medicinal mushroom Ganoderma lucidum is one of the most esteemed natural products that have been used in the traditional Chinese medicine. In this article, we demonstrate that G. lucidum triterpene extract (GLT) suppresses proliferation of human colon cancer cells HT-29 and inhibits tumor growth in a xenograft model of colon cancer. These effects of GLT are associated with the cell cycle arrest at G0/G1 and the induction of the programmed cell death Type II-autophagy in colon cancer cells. Here, we show that GLT induces formation of autophagic vacuoles and upregulates expression of Beclin-1 (1.3-fold increase) and LC-3 (7.3-fold increase) proteins in colon cancer cells and in tumors in a xenograft model (Beclin-1, 3.9-fold increase; LC-3, 1.9-fold increase). Autophagy is mediated through the inhibition of p38 mitogen-activated protein kinase (p38 MAPK) because p38 MAPK inhibitor, SB202190, induces autophagy and expression of Beclin-1 (1.2-fold increase) and LC-3 (7.4-fold increase), and GLT suppresses phosphorylation of p38 MAPK ( approximately 60% inhibition) in colon cancer cells. Taken together, our data demonstrate a novel mechanism responsible for the inhibition of colon cancer cells by G. lucidum and suggest GLT as natural product for the treatment of colon cancer.
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ABSTRACT: Ganoderma lucidum is a basidiomycetes white rot fungus belongs to the genus Ganoderma which has been used for medicinal purpose for centuries particularly in eastern countries like China, Japan & Korea. The basidiocarp, mycelia & spores of Ganoderma lucidum contain approximately 400 different bioactive compounds. The metabolites consist of mainly triterpenoids & polysaccharides & protiens. To date more than 140 triterpenoids & 200 polysaccharides have been isolated from different species Ganoderma. These compounds has been reported to have a number of pharmacological effects including immunomodulation, anti-atherosclerotic, anti-inflammatory, analgesic, chemopreventive, antitumor, chemo & radio protective, sleep promoting, antibacterial, antiviral (including anti-HIV), hypolipidemic, anti-fibrotic, hepatoprotective, anti-diabetic, anti-&rogenic, anti-angiogenic, anti-herpetic, antioxidative & radical-scavenging, anti-aging, hypoglycemic, estrogenic activity & anti-ulcer properties. The biological activities reported in Ganoderma lucidum, due to the wide range of structural diversity found in its metabolites. This review collates the publications which reported the different bioactive metabolites from this medicinal mushroom considering the most valid claim & research on biological activities of compounds.
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ABSTRACT: Medicinal mushrooms have been used for centuries as nutraceuticals to improve health and to treat numerous chronic and infectious diseases. One such mushroom is Ganoderma lucidum, commonly known as Lingzhi, a species revered as a medicinal mushroom for treating assorted diseases and prolonging life. The fungus is found in diverse locations, and this may have contributed to confusion regarding the correct taxonomic classification of the genus Ganoderma. G. lucidum was first used to name a specimen found in England and thereafter was naively applied to a different Ganoderma species found in Asia, commonly known as Chinese Lingzhi. Despite the taxonomic confusion, which has largely been uncorrected, the popularity of Lingzhi has escalated across the globe. The current taxonomic situation is now discussed accurately in this Special Issue on Ganoderma. Today it is a multi-billion dollar industry wherein Lingzhi is cultivated or collected from the wild and consumed as a tea, in alcoholic beverages, and as a nutraceutical to confer numerous health benefits. Consumption of nutraceuticals has grown in popularity, and it is becoming increasingly important that active ingredients be identified and that suppliers make substantiated health claims about their products. The objective of this article is to present a review of G. lucidum over the past 2000years from prized ancient "herbal" remedy to its use in nutraceuticals and to the establishment of a 2.5 billion $ (US) industry. Copyright © 2015 Elsevier Ltd. All rights reserved.Phytochemistry 03/2015; DOI:10.1016/j.phytochem.2015.02.015 · 3.35 Impact Factor
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ABSTRACT: Recent studies suggest that the anti‑diabetic drug metformin may reduce the risk of cancer and have anti‑proliferative effects for some but not all cancers. In this study, we examined the effects of metformin on human retinoblastoma cell proliferation in vitro and in vivo. Two different human retinoblastoma cell lines (Y79, WERI) were treated with metformin in vitro and xenografts of Y79 cells were established in nu/nu immune‑deficient mice and used to assess the effects of pharmacological levels of metformin in vivo. Metformin inhibited proliferation of the retinoblastoma cells in vitro. Similar to other studies, high concentrations of metformin (mM) blocked the cell cycle in G0‑G1, indicated by a strong decrease of G1 cyclins, especially cyclin D, cyclin‑dependent kinases (4 and 6), and flow cytometry assessment of the cell cycle. This was associated with activation of AMPK, inhibition of the mTOR pathways and autophagy marker LC3B. However, metformin failed to suppress growth of xenografted tumors of Y79 human retinoblastoma cells in nu/nu mice, even when treated with a maximally tolerated dose level achieved in human patients. In conclusion, suprapharmacological levels (mM) of metformin, well above those tolerated in vivo, inhibited the proliferation of retinoblastoma cells in vitro. However, physiological levels of metformin, such as seen in the clinical setting, did not affect the growth of retinoblastoma cells in vitro or in vivo. This suggests that the potential beneficial effects of metformin seen in epidemiological studies may be limited to specific tumor types or be related to indirect effects/mechanisms not observed under acute laboratory conditions.International Journal of Oncology 09/2014; 45(6). DOI:10.3892/ijo.2014.2650 · 2.77 Impact Factor