Inhibition of the JAK-STAT3 signaling pathway by ganoderic acid A enhances chemosensitivity of HepG2 cells to cisplatin.

Abstract

Ganoderic acid A is a lanostane triterpene isolated from Ganoderma lucidum. It has been reported to exhibit antitumor activity, which is mainly mediated through its inhibitory effect on nuclear transcription factor-kappaB and activator protein-1. But the role of ganoderic acid A in JAK-STAT3 signaling pathways is still unclear. In the present study, we investigated the effect of ganoderic acid A on the signal transducer and activator of the transcription 3 pathway and evaluated whether suppression of the signal transducer and activator of transcription 3 activity by ganoderic acid A could sensitize HepG2 cells to cisplatin. Our results show that ganoderic acid A significantly suppressed both the constitutively activated and IL-6-induced signal transducer and activator of transcription 3 phosphorylation in HepG2 cells. Inhibition of the signal transducer and activator of transcription 3 tyrosine phosphorylation was found to be achieved through suppression of JAK1 and JAK2. Furthermore, ganoderic acid A promoted cisplatin-induced cell death by enhancing the sensitivity of HepG2 cells to cisplatin mainly via the signal transducer and activator of transcription 3 suppression. These observations suggest a potential therapeutic strategy of using ganoderic acid A in combination with chemotherapeutic agents for cancer treatment.

• Authors: Xiangyang Yao, Guilan Li, Hui Xu, Chaotian Lü
• Journal: Planta medica (Planta Med) Vol. 78 Issue 16 Pg. 1740-8 (Nov 2012) ISSN: 1439-0221 [Electronic] Germany
• PMID: 22961117 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Antineoplastic Agents, Phytogenic
• Heptanoic Acids
• IL6 protein, human
• Interleukin-6
• STAT3 Transcription Factor
• STAT3 protein, human
• Lanosterol
• ganoderic acid A
• Luciferases
• JAK1 protein, human
• JAK2 protein, human
• Janus Kinase 1
• Janus Kinase 2
• Cisplatin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis
• Blotting, Western
• Cell Nucleus (metabolism)
• Cisplatin (pharmacology)
• Dose-Response Relationship, Drug
• Flow Cytometry
• Genes, Reporter
• Hep G2 Cells
• Heptanoic Acids (pharmacology)
• Humans
• Interleukin-6 (metabolism)
• Janus Kinase 1 (metabolism)
• Janus Kinase 2 (metabolism)
• Lanosterol (analogs & derivatives, pharmacology)
• Luciferases (genetics, metabolism)
• Phosphorylation
• STAT3 Transcription Factor (genetics, metabolism)
• Signal Transduction (drug effects)
• Transcriptional Activation
• Transfection