alpha-Mangostin-induced apoptosis is mediated by estrogen receptor alpha in human breast cancer cells

作者：Won Yeong Seon; Lee Ju Hye; Kwon Soon Jae; Kim Jae Yong; Park Ki Hun; Lee Mi Kyung; Seo Kwon Il^*

来源：Food and Chemical Toxicology, 2014, 66: 158-165.

DOI：10.1016/j.fct.2014.01.040

• alpha-Mangostin
• Apoptosis
• Human breast cancer cells
• Caspase
• ER alpha

In this study, we evaluated the effects of alpha-mangostin on cell growth inhibition and induction of apoptosis in MCF-7 ER alpha-positive human breast cancer cells. Our results showed that alpha-mangostin inhibited MCF-7 cell proliferation whereas ER alpha-negative MDA-MB-231 cells were less sensitive to the agent. Additionally, alpha-mangostin effectively induced apoptosis as evidenced by the appearance of apoptotic nuclei observed with Hoechst 33258 staining and evaluation of sub-G1 DNA contents by flow cytometry. alpha-Mangostin also activated caspases-8, -9, and -7; increased the protein levels of Bax, p53, and cytosolic cytochrome c; and induced PARP cleavage while reducing Bid and Bcl-2 protein expression. In addition, apoptosis-inducing factor (AIF) was transported from mitochondria to the cytosol after alpha-mangostin treatment. alpha-mangostin also induced apoptosis in 17-beta-estradiol (E2)-stimulated MCF-7 cells in parallel with the non-stimulated cells. Moreover, treatment with 10 mu M alpha-mangostin for 48 h specifically decreased the expression of ER alpha and pS2, an estrogen-responsive gene, in MCF-7 cells. Furthermore, knockdown of ER alpha expression in MCF-7 cells with siRNA attenuated alpha-mangostin-induced cell growth inhibition and caspase-7 activation. These results suggest that ER alpha is required for alpha-mangostin-induced growth inhibition and apoptosis in human breast cancer cells. Therefore, alpha-mangostin may be used to prevent and treat of ER-positive breast cancer.

• 出版日期2014-4