α-Mangostin-induced apoptosis is mediated by estrogen receptor α in human breast cancer cells.
In this study, we evaluated the effects of α-mangostin on cell growth inhibition and induction of apoptosis in MCF-7 ERα-positive human breast cancer cells. Our results showed that α-mangostin inhibited MCF-7 cell proliferation whereas ERα-negative MDA-MB-231 cells were less sensitive to the agent. Additionally, α-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. α-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 α-mangostin treatment. α-mangostin also induced apoptosis in 17-β-estradiol (E2)-stimulated MCF-7 cells in parallel with the non-stimulated cells. Moreover, treatment with 10μM α-mangostin for 48h specifically decreased the expression of ERα and pS2, an estrogen-responsive gene, in MCF-7 cells. Furthermore, knockdown of ERα expression in MCF-7 cells with siRNA attenuated α-mangostin-induced cell growth inhibition and caspase-7 activation. These results suggest that ERα is required for α-mangostin-induced growth inhibition and apoptosis in human breast cancer cells. Therefore, α-mangostin may be used to prevent and treat of ER-positive breast cancer.
Department of Food and Nutrition, Sunchon National University, Suncheon 540-950, Republic of Korea; Department of Bioscience and Biotechnology, Kyushu University, Fukuoka 812-8581, Japan.
Yeong-Seon
YS
Won
Department of Food and Nutrition, Sunchon National University, Suncheon 540-950, Republic of Korea.
Ju-Hye
JH
Lee
School of Food Science and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
Soon-Jae
SJ
Kwon
Jeonnam Institute of National Resources Research, Jangheung 529-851, Republic of Korea.
Jae-Yong
JY
Kim
Division of Applied Life Science, IALS, Graduate School of Gyeongsang National University, Jinju 660-701, Republic of Korea.
Ki-Hun
KH
Park
Department of Food and Nutrition, Sunchon National University, Suncheon 540-950, Republic of Korea.
Mi-Kyung
MK
Lee
Department of Food and Nutrition, Sunchon National University, Suncheon 540-950, Republic of Korea. Electronic address: seoki@sunchon.ac.kr.
Kwon-Il
KI
Seo
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D047628:Estrogen Receptor alpha / Q000502:physiology*; D006801:Humans; D061986:MCF-7 Cells; D051381:Rats; D044004:Xanthones / Q000494:pharmacology*
D047628:Estrogen Receptor alpha; D044004:Xanthones; C021053:mangostin
Apoptosis; Caspase; ERα; Human breast cancer cells; α-Mangostin