Silibinin induces protective superoxide generation in human breast cancer MCF-7 cells.
The pharmacological activity of polyphenolic silibinin from milk thistle (Silybum marianum) is primarily due to its antioxidant property. However, this study found that silibinin promoted sustained superoxide (O(2)(.-)) production that was specifically scavenged by exogenous superoxide dismutase (SOD) in MCF-7 cells, while the activity of endogenous SOD was not changed by silibinin. Previous work proved that silibinin induced MCF-7 cell apoptosis through mitochondrial pathway and this study further proved that O(2)(.-) generation induced by silibinin was also related to mitochondria. It was found that respiratory chain complexes I, II and III were all involved in silibinin-induced O(2)(.-) generation. Moreover, it was found that silibinin-induced O(2)(.-) had protective effect, as exogenous SOD markedly enhanced silibinin-induced apoptosis.
Wang
Hong-Jun
HJ
China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
Jiang
Yuan-Yuan
YY
Wei
Xiao-Feng
XF
Huang
Huai
H
Tashiro
Shin-Ichi
S
Onodera
Satoshi
S
Ikejima
Takashi
T
D000975:Antioxidants / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D012838:Silymarin; D013481:Superoxides; D000077385:Silybin; D011505:Protein-Tyrosine Kinases; D048051:p38 Mitogen-Activated Protein Kinases