A novel antioestrogen agent (3R,6R)-bassiatin inhibits cell proliferation and cell cycle progression by repressing cyclin D1 expression in 17β-oestradiol-treated MCF-7 cells.
Bassiatin [(3R,6R)-bassiatin] was isolated from the endogenous fungus Fusarium oxysporum J8-1-2. We found that oestrogen-dependent cell growth was inhibited by bassiatin in MCF-7 ERα (oestrogen receptor α)-positive breast cancer cells. In addition, the mRNA and protein levels of ERα and the oestrogen-responsive gene cyclin D1 were down-regulated by bassiatin in the presence of 17β-oestradiol. Co-treatment of 17β-oestradiol and bassiatin increased phospho-cyclin D1 (Thr286), an indicator of cyclin D1 phosphorylation-dependent degradation. However, this effect was not obvious in the absence of 17β-oestradiol, suggesting that bassiatin may play a role in the metabolism of cyclin D1 by decreasing cyclin D1 protein expression in the presence of 17β-oestradiol. Cyclin D1, known as a key cell cycle regulator, regulates the transition of G1- and S-phase. Decreased cyclin D1 was found to be involved in bassiatin-induced MCF-7 cell cycle arrest. Collectively, our study showed that bassiatin induced cell cycle arrest and exerted an antioestrogen effect. It may prove to be a potential drug target for antioestrogen therapy in ERα-positive breast cancer.
Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, Peoples Republic of China.
Li
L
Meng
Bo
B
Feng
Hongwen
H
Tao
Tingting
T
Yang
Yan
Y
Meng
Weiming
W
Zhu
Caiguo
C
Huang
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000737:chemistry / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005670:Fusarium / Q000737:chemistry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D009025:Morpholines / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation; D016196:S Phase / Q000187:drug effects; D013237:Stereoisomerism
D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D009025:Morpholines; D019938:Cyclin D1; D004958:Estradiol; C085610:lateritin