Targeting silibinin in the antiproliferative pathway.
BACKGROUND
Due to the failure and severe toxicity of cancer chemotherapy, silibinin, a natural flavonoid from the seeds of milk thistle, has recently received more attention for its potential anticancer and nontoxic roles in animals and humans. Silibinin has clearly demonstrated inhibition of multiple cancer cell signaling pathways, including growth inhibition, inhibition of angiogenesis, chemosensitization, and inhibition of invasion and metastasis. Cumulative evidence implicates that silibinin is a potential agent for cancer chemoprevention and chemotherapy.


METHODS
Our aim is to discuss the recent progress of silibinin in regulating multiple anticancer proliferative signaling pathways; the review covers literature mainly from the past 3 - 5 years.


RESULTS
One of the strategies for tumor therapy is eradication of cancer cells through targeting specific cell-proliferative pathways. This review highlights the current knowledge of silibinin in regulating multiple cellular proliferative pathways in cancer cells, including receptor tyrosine kinases, androgen receptor, STATs, NF-kappaB, cell cycle regulatory and apoptotic signaling pathways.


CONCLUSIONS
The molecular mechanisms of silibinin-mediated antiproliferative effects are mainly via receptor tyrosine kinases, androgen receptor, STATs, NF-kappaB, cell cycle regulatory and apoptotic signaling pathways in various cancer cells. Targeting inhibition of proliferative pathways through silibinin treatment may provide a new approach for improving chemopreventive and chemotherapeutic effects.
Li
Lei
L
The First Hospital of Xi'an Jiaotong University, Department of Urology, 277 Yanta West Road, Xi'an 710061, People's Republic of China.
Zeng
Jin
J
Gao
Ye
Y
He
Dalin
D
D059002:Androgen Receptor Antagonists; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D049109:Cell Proliferation / Q000187:drug effects*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems / Q000379:methods*; D005419:Flavonoids / Q000737:chemistry; D006801:Humans; D020944:Silybum marianum; D008954:Models, Biological; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008517:Phytotherapy; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology / Q000627:therapeutic use
D059002:Androgen Receptor Antagonists; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D005419:Flavonoids; D016328:NF-kappa B; D050791:STAT Transcription Factors; D012838:Silymarin; D000077385:Silybin; D020794:Receptor Protein-Tyrosine Kinases