ERK1/2 and Akt pathway activated during (3R,6R)-bassiatin(1)-induced apoptosis in MCF-7 cells

作者：Meng Li; Tao Hongwen; Dong Guoqiang; Yang Tingting; Zhang Wannian; Zhu Weiming^*; Huang Caiguo

来源：Cell Biology International, 2012, 36(4): 345-348.

DOI：10.1042/CBI20110388

• Akt
• breast cancer
• oestrogen receptor alpha (ER alpha)
• extracellular-signal-regulated kinase (ERK)
• (3R
• 6R)-bassiatin(1)

(3R,6R)-bassiatin(1) was isolated from the endogenous fungus, Fusarium oxysporum J8-1-2. Previous studies showed that (3R,6R)-bassiatin(1) has anti-oestrogen properties which make it cytotoxic to ER (oestrogen receptor)-positive breast cancer cells (MCF-7) by cell cycle arrest and induction of apoptosis. (3R,6R)-bassiatin(1) suppresses mRNA and protein expression of the ER alpha and oestrogen responsive genes of cyclin D1 and PR. We have investigated the interaction between (3R,6R)-bassiatin(1) and ER alpha and followed the roles of ERK (extracellular-signal-regulated kinase), Akt and GSK3 beta (glycogen synthase kinase 3 beta) during (3R,6R)-bassiatin(1)-induced apoptosis of MCF-7 cells. (3R,6R)-bassiatin(1) competed with E2 (17 beta-estradiol) for ER alpha active sites to inhibit ER alpha activation. However, while ERK1/2 and Akt were activated, GSK3 beta was inactivated during (3R,6R)-bassiatin(1)-induced apoptosis, suggesting that this compound is indeed an anti-oestrogen agent that can also activate the survival signalling pathway. Apoptosis caused by (3R,6R)-bassiatin(1) may be related to activation of ERK.

• 出版日期2012-4
• 单位中国人民解放军第二军医大学; 中国海洋大学