Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation.
Breast cancer is the most common cancer in women. Bisphenol A (BPA), as a known endocrine disrupter, is closely related to the development of breast cancer. Curcumin has been clinically used in chemopreventation and treatment of cancer; however, it remains unknown whether microRNAs are involved in curcumin-mediated protection from BPA-associated promotive effects on breast cancer. In the present study, we showed that BPA exhibited estrogenic activity by increasing the proliferation of estrogen-receptor-positive MCF-7 human breast cancer cells and triggering transition of the cells from G1 to S phase. Curcumin inhibited the proliferative effects of BPA on MCF-7 cells. Meanwhile, BPA-induced upregulation of oncogenic miR-19a and miR-19b, and the dysregulated expression of miR-19-related downstream proteins, including PTEN, p-AKT, p-MDM2, p53, and proliferating cell nuclear antigen, were reversed by curcumin. Furthermore, the important role of miR-19 in BPA-mediated MCF-7 cell proliferation was also illustrated. These results suggest for the first time that curcumin modulates miR-19/PTEN/AKT/p53 axis to exhibit its protective effects against BPA-associated breast cancer promotion. Findings from this study could provide new insights into the molecular mechanisms by which BPA exerts its breast-cancer-promoting effect as well as its target intervention.
Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Xiaoting
X
Li
Wei
W
Xie
Chunfeng
C
Xie
Cong
C
Huang
Jianyun
J
Zhu
Zhaofeng
Z
Liang
Feifei
F
Deng
Mingming
M
Zhu
Weiwei
W
Zhu
Rui
R
Wu
Jieshu
J
Wu
Shanshan
S
Geng
Caiyun
C
Zhong
D001559:Benzhydryl Compounds; D001943:Breast Neoplasms / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010636:Phenols; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D003474:Curcumin; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D010636:Phenols; D051057:Proto-Oncogene Proteins c-akt; D016159:Tumor Suppressor Protein p53; C549214:MIRN19A microRNA, human; C495901:TP53 protein, human; C494929:PTEN protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
MCF-7 breast cancer cells; bisphenol A; curcumin; inhibition; miR-19; proliferation