Targeting signal transducer and activator of transcription 3 contributes to the solamargine-inhibited growth and -induced apoptosis of human lung cancer cells.
Solamargine (SM), a major steroidal alkaloid glycoside extracted from a traditional Chinese medicinal herb, Solanum nigrum L. (SNL), has been shown to inhibit growth and induce apoptosis of various cancer cells. However, the molecular mechanisms underlying this are poorly understood. In this study, we showed that SM inhibited growth and induced apoptosis of non-small-cell lung cancer (NSCLC) cells in a time- and dose-dependent manner. To further explore this, we found that SM increased phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in a time-dependent fashion. SM also inhibited phosphorylation and protein expression of signal transducer and activator of transcription 3 (Stat3), a transcription factor, which was abrogated by the SB203580, a specific inhibitor of p38 MAPK. In addition, SM induced protein expression of p21, one of cyclin-dependent kinase inhibitors, and this was not observed in cell overexpression of Stat3 or cells treated with SB203580. Finally, while silencing of Stat3 had no further effect, exogenous expression of Stat3 overcame the effect of SM on cell proliferation. Collectively, our results show that SM inhibits proliferation and induces apoptosis in lung cancer cells through p38 MAPK-mediated suppression of phosphorylation and protein expression of Stat3, followed by inducing Stat3 downstream effector p21. This unveils a potential new mechanism by which SM inhibits growth of human lung cancer cells.
Laboratory of Tumor Molecular Biology and Targeted Therapies, University of Guangzhou Traditional Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, 4th Floor, Scientific Research Building, Neihuan West Road No. 55, University City, Panyu District, Guangzhou, Guangdong Province, 510006, People's Republic of China.
Yan
Y
Zhou
Qing
Q
Tang
Shunyu
S
Zhao
Fang
F
Zhang
Liuning
L
Li
WanYin
W
Wu
ZhiYu
Z
Wang
Swei
S
Hann
D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D012991:Solanaceous Alkaloids / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012991:Solanaceous Alkaloids; C026609:beta-solamarine; D048051:p38 Mitogen-Activated Protein Kinases