Biography:
Abstract:
Background: Garcinol, a polyisoprenylated benzophenone isolated from fruiting bodies of Garcinia indica, and possessing anti-inflammatory, antioxidant, acetyltransferase inhibitory and anticancer activities. our perviously work has demonstrated α7-nAChR drives the progression and recurrence of HCC through JAK2/STAT3 signaling, which has been linked with proliferation, survival, invasion and angiogenesis, and might be a novel target for anti-HCC therapy. Thus, novel agents that can suppress α7-nAChR activation have potential for both prevention and treatment of HCC. Here we report, garcinol, could suppress α7-nAChR and downregulated JAK2/STAT3 axis in vitro and in vivo model of HCC.
Methods: Two HCC cell lines have been treated with garcinol and the inhibition of expression of α7-nAChR have been checked by immunoblotting, immuno-fluorescence, and RT-PCR. Xenografted tumor model has been generated in nude mice using HCC cell line and effect of garcinol in the inhibition of tumor growth has been investigated.
Results: Garcinol inhibit α7-nAChR and downstream JAK2/STAT-3 expression in Mahlavu and Hep-J5 cancer cell lines and was also found to inhibit cell proliferation, invasion, migration and lower the tumor’s sphere-formation ability. Western blot and real-time PCR further evaluated the expression of α7-nAChR. These results is consist with our previously work on inhibition of α7-nAChR via siRNA. We further verified in vivo using human HCC xenograft tumors in nude mice, where administration of garcinol significantly inhibited tumor growth, improved overall survival, and western blot analysis of remnant tumor lysates showed reduced α7-nAChR expression and activation.
Conclusion: Together, these study suggested garcinol exerts its anti-proliferative and pro-apoptotic effects through suppression of α7-nAChR and downregulated JAK2/STAT3 signaling in HCC both in vitro and in vivo.
Keywords: Garcinol, α7-nAChR, nicotine receptor, JAK2, Hepatocellular carcinoma