α-Mangostin-induced apoptosis is mediated by estrogen receptor α in human breast cancer cells
Yeong-Seon Won1, Ju-Hye Lee2, Soon-Jae Kwon3
1Department of Food and Nutrition, Sunchon National University, Suncheon 540-950, Republic of Korea; Department of Bioscience and Biotechnology, Kyushu University, Fukuoka 812-8581, Japan.
Abstract:
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.
Insights
Alpha-mangostin inhibits growth and induces apoptosis in ERα-positive breast cancer cells. Estrogen receptor alpha (ERα) is crucial for these effects, suggesting alpha-mangostin
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Estrogen receptor-positive (ERα) breast cancer is a major health concern.
- Targeting ERα signaling is a key therapeutic strategy.
- Natural compounds offer potential for novel cancer treatments.
Purpose of the Study:
- To investigate the effects of alpha-mangostin on ERα-positive human breast cancer cells.
- To elucidate the role of ERα in alpha-mangostin's anti-cancer activity.
Main Methods:
- Cell proliferation assays using MCF-7 and MDA-MB-231 cell lines.
- Apoptosis induction assessment via Hoechst staining and flow cytometry.
- Western blot analysis of apoptosis-related proteins (Bax, p53, Bcl-2, caspases, Bid, PARP).
- Estrogen receptor alpha (ERα) knockdown using siRNA.
Main Results:
- Alpha-mangostin inhibited MCF-7 cell proliferation and induced apoptosis.
- ERα-negative MDA-MB-231 cells showed less sensitivity to alpha-mangostin.
- Alpha-mangostin activated caspases, increased pro-apoptotic proteins, and decreased anti-apoptotic proteins.
- ERα knockdown attenuated alpha-mangostin's growth inhibitory and apoptotic effects.
Conclusions:
- Alpha-mangostin exhibits potent anti-cancer properties against ERα-positive breast cancer.
- ERα is essential for alpha-mangostin's efficacy in inhibiting cell growth and inducing apoptosis.
- Alpha-mangostin holds promise as a therapeutic agent for ER-positive breast cancer.
