AIMS: Trichosanthin (TCS) is a type I ribosome-inactivating protein (RIP) with antitumor activities for various cancers. In this paper, we aimed to investigate whether dexamethasone, an important synthetic member of the glucocorticoid steroids, in combination with TCS can be a potential therapy in treating hepatoma. MAIN METHODS: Cell viability was investigated using MTT assay, and apoptosis was evaluated with Hoechst 33258 staining. Western blot analysis was used to examine the changes in the expression levels of IkappaB-alpha, NF-kappaB p65 subunit and Cox-2. Additionally, we took advantage of dominant-negative IkappaB (IkappaB-DM) over-expression and chemical inhibitor PDTC to inhibit NF-kappaB activation. KEY FINDINGS: Our results demonstrated that dexamethasone could enhance TCS-induced apoptosis in the hepatoma cell line HepG2, decreasing IC50 values from in excess of 200microg/ml to 50microg/ml. In addition, our results demonstrated that TCS could induce rapid degradation of IkappaB-alpha, nuclear translocation of NF-kappaB and decrease of COX-2 expression in HepG2 cells. Inhibition of NF-kappaB by biological (IkappaB-DM) or chemical inhibitor (PDTC) increased HepG2 cells' sensitivity to TCS, resulting in cell viability rate decreasing and apoptotic rate increasing. Simultaneously, dexamethasone increased the level of IkappaB-alpha protein and effectively inhibited TCS-induced degradation of IkappaB-alpha. SIGNIFICANCE: These results suggest that dexamethasone could enhance trichosanthin-induced apoptosis in the HepG2, at least in part, by inhibiting the NF-kappaB signaling pathway and thus strengthening the antitumor effects of TCS, which highlights the possibility of combined drug application of TCS and dexamethasone in the clinical treatment of hepatoma.
AIMS: Trichosanthin (TCS) is a type I ribosome-inactivating protein (RIP) with antitumor activities for various cancers. In this paper, we aimed to investigate whether dexamethasone, an important synthetic member of the glucocorticoid steroids, in combination with TCS can be a potential therapy in treating hepatoma. MAIN METHODS: Cell viability was investigated using MTT assay, and apoptosis was evaluated with Hoechst 33258 staining. Western blot analysis was used to examine the changes in the expression levels of IkappaB-alpha, NF-kappaB p65 subunit and Cox-2. Additionally, we took advantage of dominant-negative IkappaB (IkappaB-DM) over-expression and chemical inhibitor PDTC to inhibit NF-kappaB activation. KEY FINDINGS: Our results demonstrated that dexamethasone could enhance TCS-induced apoptosis in the hepatoma cell line HepG2, decreasing IC50 values from in excess of 200microg/ml to 50microg/ml. In addition, our results demonstrated that TCS could induce rapid degradation of IkappaB-alpha, nuclear translocation of NF-kappaB and decrease of COX-2 expression in HepG2 cells. Inhibition of NF-kappaB by biological (IkappaB-DM) or chemical inhibitor (PDTC) increased HepG2 cells' sensitivity to TCS, resulting in cell viability rate decreasing and apoptotic rate increasing. Simultaneously, dexamethasone increased the level of IkappaB-alpha protein and effectively inhibited TCS-induced degradation of IkappaB-alpha. SIGNIFICANCE: These results suggest that dexamethasone could enhance trichosanthin-induced apoptosis in the HepG2, at least in part, by inhibiting the NF-kappaB signaling pathway and thus strengthening the antitumor effects of TCS, which highlights the possibility of combined drug application of TCS and dexamethasone in the clinical treatment of hepatoma.
Authors: Evandro Fei Fang; Chris Zhi Yi Zhang; Lin Zhang; Jack Ho Wong; Yau Sang Chan; Wen Liang Pan; Xiu Li Dan; Cui Ming Yin; Chi Hin Cho; Tzi Bun Ng Journal: PLoS One Date: 2012-09-05 Impact factor: 3.240
Authors: Ga Bin Park; Yunock Choi; Yeong Seok Kim; Hyun-Kyung Lee; Daejin Kim; Dae Young Hur Journal: Int J Oncol Date: 2013-05-20 Impact factor: 5.650