title: 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.affiliation: Department of Biology and Food Engineering, Bengbu College, Bengbu, PR China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Yao
authors.forename: Guilan
authors.initials: G
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Chaotian
authors.initials: C
authors.lastname: Lü
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D053613:Janus Kinase 1 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism*; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006538:Heptanoic Acids; C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007810:Lanosterol; C515005:ganoderic acid A; D008156:Luciferases; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D002945:Cisplatin