Apoptosis induction by alantolactone in breast cancer MDA-MB-231 cells through reactive oxygen species-mediated mitochondrion-dependent pathway
Cui Li, Bu Weiquan, Song Jie, Feng Liang, Xu Tingting, Liu Dan, Ding Wenbo, Wang Jianhua, Li Changyang, Ma Binge, Luo Yi, Jiang Ziyu, Wang Chengcheng, Chen Juan, Hou Jian, Yan Hongmei, Yang Lei, Jia Xiaobin,
소속 상세정보
( Cui Li )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
( Bu Weiquan )
Jiangsu Province Academy of Chinese Medicine Key Laboratory of New Drug Delivery System of Chinese Meteria Medica
( Song Jie )
Jiangsu Province Academy of Chinese Medicine Key Laboratory of New Drug Delivery System of Chinese Meteria Medica
( Feng Liang )
Jiangsu Province Academy of Chinese Medicine Key Laboratory of New Drug Delivery System of Chinese Meteria Medica
( Xu Tingting )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
( Liu Dan )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
( Ding Wenbo )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
( Wang Jianhua )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
( Li Changyang )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
( Ma Binge )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
( Luo Yi )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
( Jiang Ziyu )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
( Wang Chengcheng )
Jiangsu Province Academy of Chinese Medicine Key Laboratory of New Drug Delivery System of Chinese Meteria Medica
( Chen Juan )
Jiangsu Province Academy of Chinese Medicine Key Laboratory of New Drug Delivery System of Chinese Meteria Medica
( Hou Jian )
Jiangsu Province Academy of Chinese Medicine Key Laboratory of New Drug Delivery System of Chinese Meteria Medica
( Yan Hongmei )
Jiangsu Province Academy of Chinese Medicine Key Laboratory of New Drug Delivery System of Chinese Meteria Medica
( Yang Lei )
Jiangsu Province Academy of Chinese Medicine Key Laboratory of New Drug Delivery System of Chinese Meteria Medica
( Jia Xiaobin )
Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine
Abstract
Alantolactone is a sesquiterpene lactone isolated from Inula helenium L. Although alantolactone possesses anti-inflammation and apoptosis-induction activities, the underlying mechanism of anti-cancer effect on human breast cancer cells remains largely unknown. In this study, we explored the possibility of alantolactone as an apoptosis-inducing cytotoxic agent using MDA-MB-231 cells as in vitro model. Alantolactone significantly induced its apoptosis, demonstrated by cell cycle analysis, annexin V-APC/7-AAD double staining and dUTP nick end labeling. Additionally, alantolactone triggered the mitochondrial-mediated caspase cascade apoptotic pathway, which was confirmed by increased Bax/Bcl-2 ratio, loss of MMP, release of cytc from mitochondria to cytoplasm, activation of caspase 9/3, and subsequent cleavage of PARP. Z-VAD-FMK partially prevented apoptosis induced by alantolactone. Alantolactone provoked the production of ROS, while NAC (a scavenger of ROS) reversed alantolactone-mediated depolarization of MMP and apoptosis. Alantolactone modulated the activities of MAPKs. As expected, cotreatment with SB203580, SP600125 or U0126 could reduced the apoptotic rate. Furthermore, alantolactone decreased the protein expressions of p-NF-kB p65 and p-STAT3, increased p-c-Jun level in a dose-dependent manner. These findings suggested that alantolactone possessed anticancer activity via ROS-mediated mitochondrial dysfunction involving MAPK pathway, and had an effect on the transcription factors of NF-kB, AP-1 and STAT3.
키워드
Alantolactone; Apoptosis; Reactive oxygen species; Mitochondria; MAPK
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