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Planta Med 2012; 78(16): 1740-1748
DOI: 10.1055/s-0032-1315303
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Inhibition of the JAK-STAT3 Signaling Pathway by Ganoderic Acid A Enhances Chemosensitivity of HepG2 Cells to Cisplatin

Xiangyang Yao
1   Department of Biology and Food Engineering, Bengbu College, Bengbu, PR China
,
Guilan Li
2   Jiangsu Province Key Laboratory for Molecular and Medicine Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, PR China
,
Hui Xu
1   Department of Biology and Food Engineering, Bengbu College, Bengbu, PR China
,
Chaotian Lü
1   Department of Biology and Food Engineering, Bengbu College, Bengbu, PR China
› Author Affiliations
Further Information

Publication History

received 01 May 2012
revised 28 July 2012

accepted 07 August 2012

Publication Date:
07 September 2012 (online)

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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.

Key words

ganoderic acid A - STAT3 - chemosensitivity - cisplatin - Ganoderma lucidum - Aphyllophoromycetideae
 

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