Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells

Abstract Constitutive activation of STAT3 has been shown in several human cancers and transformed cell lines including hepatocellular carcinoma (HCC). In the present report, we investigated whether diosgenin, a steroidal saponin isolated from fenugreek can modulate the STAT3 signaling pathway. We fo...

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Bibliographic Details
Published in:Cancer letters 2010-06, Vol.292 (2), p.197-207
Main Authors: Li, Feng, Fernandez, Prasana Priscilla, Rajendran, Peramaiyan, Hui, Kam M, Sethi, Gautam
Format: Article
Language:English
Subjects:
Angiogenesis
Antibiotics
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Biomedical research
Blotting, Western
Breast cancer
Cancer therapies
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cell culture
Cell Line, Tumor
Cell Proliferation - drug effects
Councils
Diosgenin
Diosgenin - pharmacology
Dose-Response Relationship, Drug
Doxorubicin - pharmacology
Drug dosages
Flow Cytometry
Gene expression
Hematology, Oncology and Palliative Medicine
Hepatocellular carcinoma
Humans
Immunohistochemistry
JAK2
Kinases
Liver cancer
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Paclitaxel - pharmacology
Phosphorylation
Proteins
Proto-Oncogene Proteins c-akt - metabolism
Rodents
Signal Transduction - drug effects
STAT3
STAT3 Transcription Factor - metabolism
Tumorigenesis
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Summary:Abstract Constitutive activation of STAT3 has been shown in several human cancers and transformed cell lines including hepatocellular carcinoma (HCC). In the present report, we investigated whether diosgenin, a steroidal saponin isolated from fenugreek can modulate the STAT3 signaling pathway. We found that diosgenin inhibited both constitutive and inducible activation of STAT3 with no effect on STAT5. The activation of c-Src, JAK1 and JAK2 implicated in STAT3 activation, were also suppressed by this saponin. Pervanadate reversed the diosgenin-induced downregulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that diosgenin can induce the expression of Src homology 2 phosphatase 2 (SH-PTP2) that correlated with downregulation of constitutive STAT3 activation. Diosgenin also downregulated the expression of various STAT3-regulated gene products, inhibited proliferation and potentiated the apoptotic effects of paclitaxel and doxorubicin. Overall, these results suggest that diosgenin is a novel blocker of the STAT3 activation pathway, with a potential role in the treatment of HCC and other cancers.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2009.12.003