Ganoderic acid DM, a natural triterpenoid, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells
ABSTRACT Ganoderic acid DM (GADM) is a triterpenoid isolated from Ganoderma lucidum, a well-known edible medicinal mushroom. In the present study, we found that GADM effectively inhibited cell proliferation and colony formation in MCF-7 human breast cancer cells, which was much stronger than that of MDA-MB-231 breast cancer cells. GADM both concentration- and time-dependently mediated G1 cell cycle arrest and significantly decreased the protein level of CDK2, CDK6, cycle D1, p-Rb and c-Myc in MCF-7 cells. Moreover, GADM obviously induced DNA fragmentation and cleavage of PARP which are the characteristics of apoptosis and decreased the mitochondrial membrane potential in MCF-7 cells. Besides, we also showed that GADM elicited DNA damage as measured by comet assay which is a sensitive method for DNA damage detection. γ-H2AX, a marker of DNA damage, was also slightly up-regulated after treated with GADM for 6h, suggesting that the G1 cell cycle arrest and apoptosis induced by GADM may be partially resulted from GADM-induced DNA damage. These results have advanced our current understandings of the anti-cancer mechanisms of GADM.
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ABSTRACT: Cancer is the second leading cause of death worldwide. Edible medicinal mushrooms have been used in traditional medicine as regimes for cancer patients. Recently anti-cancer bioactive components from some mushrooms have been isolated and their anti-cancer effects have been tested. Pleurotus ferulae, a typical edible medicinal mushroom in Xinjiang China, has also been used to treat cancer patients in folk medicine. However, little studies have been reported on the anti-cancer components of Pleurotus ferulae. This study aims to extract bioactive components from Pleurotus ferulae and to investigate the anti-cancer effects of the extracts. We used ethanol to extract anti-cancer bioactive components enriched with terpenoids from Pleurotus ferulae. We tested the anti-tumour effects of ethanol extracts on the melanoma cell line B16F10, the human gastric cancer cell line BGC 823 and the immortalized human gastric epithelial mucosa cell line GES-1 in vitro and a murine melanoma model in vivo. Cell toxicity and cell proliferation were measured by MTT assays. Cell cycle progression, apoptosis, caspase 3 activity, mitochondrial membrane potential (MMP), migration and gene expression were studied in vitro. PFEC suppressed tumor cell growth, inhibited cell proliferation, arrested cells at G0/G1 phases and was not toxic to non-cancer cells. PFEC also induced cell apoptosis and necrosis, increased caspase 3 activity, reduced the MMP, prevented cell invasion and changed the expression of genes associated with apoptosis and the cell cycle. PFEC delayed tumor formation and reduced tumor growth in vivo. In conclusion, ethanol extracted components from Pleurotus ferulae exert anti-cancer effects through direct suppression of tumor cell growth and invasion, demonstrating its therapeutic potential in cancer treatment.PLoS ONE 07/2014; 9(7):e102673. DOI:10.1371/journal.pone.0102673 · 3.53 Impact Factor
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ABSTRACT: Panax ginseng is traditionally used as a remedy for cancer, inflammation, stress and aging, and ginsenoside‑Rg5 is a major bioactive constituent of steamed ginseng. The present study aimed to evaluate whether ginsenoside‑Rg5 had any marked cytotoxic, apoptotic or DNA‑damaging effects in human cervical cancer cells. Five human cervical cancer cell lines (HeLa, MS751, C33A, Me180 and HT‑3) were used to investigate the cytotoxicity of ginsenoside‑Rg5 using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. Additionally, the effects of ginsenoside‑Rg5 on the apoptosis of HeLa and MS751 cells were detected using DNA ladder assays and flow cytometry. DNA damage was assessed in the HeLa and MS751 cells using alkaline comet assays and by detection of γH2AX focus formation. The HeLa and MS751 cells were significantly more sensitive to ginsenoside‑Rg5 treatment compared with the C‑33A, HT‑3 and Me180 cells. As expected, ginsenoside‑Rg5 induced significant concentration‑ and time‑dependent increases in apoptosis. In addition, ginsenoside‑Rg5 induced significant concentration‑dependent increases in the level of DNA damage compared with the negative control. Consistent with the comet assay data, the percentage of γH2AX‑positive HeLa and MS751 cells also revealed that ginsenoside‑Rg5 caused DNA double‑strands to break in a concentration‑dependent manner. In conclusion, ginsenoside‑Rg5 had marked genotoxic effects in the HeLa and MS751 cells and, thus, demonstrates potential as a genotoxic or cytotoxic drug for the treatment of cervical cancer.Molecular Medicine Reports 10/2014; DOI:10.3892/mmr.2014.2821 · 1.48 Impact Factor
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ABSTRACT: Recent studies have found that triterpene acid type compounds has many effects including antiinflammatory, regulating blood sugar level, antiviral and antitumor activity. More importantly, triterpene acid type compounds has become one of the most popular topics recently because its selective toxic effects on cancer cells and harmless to normal cells at the same time. This review summarized the antitumor activity and the mechanism of triterpene acid type compounds, providing guideline for further research and development of new antitumor natural products.Journal of Cancer Research and Therapeutics 08/2014; 10 Suppl(5):C14-9. DOI:10.4103/0973-1482.139746 · 0.95 Impact Factor