α-Mangostin suppresses human gastric adenocarcinoma cells in vitro via blockade of Stat3 signaling pathway

• Published in: Acta pharmacologica Sinica Vol. 35; no. 8; pp. 1065 - 1073
• Main Authors: Shan, Tao, Cui, Xi-juan, Li, Wei, Lin, Wan-run, Lu, Hong-wei, Li, Yi-ming, Chen, Xi, Wu, Tao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2014; Nature Publishing Group
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; BGC-823; Biomedical and Life Sciences; Biomedicine; Cell Line, Tumor; Cell Survival - drug effects; Garcinia mangostana - chemistry; Humans; Immunology; Internal Medicine; Medical Microbiology; Original; original-article; Pharmacology/Toxicology; Signal Transduction - drug effects; Stat3; STAT3 Transcription Factor - antagonists & inhibitors; STAT3 Transcription Factor - metabolism; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Vaccine; Xanthones - isolation & purification; Xanthones - pharmacology; 体外; 信号转导通路; 抗肿瘤作用; 时间依赖性; 胃癌细胞; 路阻; mangosteen; anti-cancer drug; Mcl-1; Bcl-xL; gastric adenocarcinoma; α-mangostin; mitochondria; Stat3; apoptosis
• ISSN: 1671-4083; 1745-7254
• DOI: 10.1038/aps.2014.43

Aim： To investigate the anti-tumor effects of α-mangostin, a major xanthone identified in the pericarp of mangosteen （Garcinia mangostana Linn）, against human gastric adenocarcinoma cells in vitro, and the mechanisms of the effects. Methods： Human gastric adenocarcinoma cell lines BGC-823 and SGC-7901 were treated with α-mangostin. The cell viability was measured with MTT assay, and cell apoptosis was examined using flow cytometry and TUNEL assay. The expression of the relevant proteins was detected using Western blot. Results： Treatment with α-mangostin （3-10 μg/mL） inhibited the viability of both BGC-823 and SGC-7901 cells in dose- and time- manners. Furthermore, α-mangostin （7 μg/mL） time-dependently increased the apoptosis index of the cancer cells, reduced the mitochondrial membrane potential of the cancer cells, and significantly increased the release of cytochrome c and AIF into cytoplasm Moreover, theα-mangostin treatment markedly suppressed the constitutive Stat3 protein activation, and Stat3-regulated Bcl-xL and Mcl-1 protein levels in the cancer cells. Conclusion： The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to blockade of Stat3 signaling pathway.