Ganoderic acid DM, a natural triterpenoid, induces DNA damage, G1 cell cycle arrest and apoptosis in human breast cancer cells
2011; Elsevier BV; Volume: 83; Issue: 2 Linguagem: Inglês
10.1016/j.fitote.2011.12.004
ISSN1873-6971
AutoresGuosheng Wu, Jin‐Jian Lu, Jiajie Guo, Ying‐Bo Li, Wen Siang Tan, Yuanye Dang, Zhangfeng Zhong, Zengtao Xu, Xiuping Chen, Yitao Wang,
Tópico(s)Phytochemistry and Bioactivity Studies
ResumoGanoderic 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 6 h, 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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