The anti-cancerous activity of recombinant trichosanthin on prostate cancer cell PC3

Abstract

ContextTrichosanthin produced in the root tube of Trichosanthes kirilowii shows anti-tumor activity on a series of cancer cells including Hela, MCF-7, HL-60. But there is little information about its effect on the carcinogenesis of prostate cancer.ObjectiveThis work was designed to study the role of trichosanthin on prostate cancer cells PC3.Materials and methodsTrichosanthin was expressed in BL21 strain and purified by affinity chromatography. MTT assay was designed to determine the effect of trichosanthin on growth of PC3 cells at doses of 10, 20, 40, 60, 80, and 120 μg/ml. Then the effect of 50 μg/ml rTCS alone or combined with 2 μM IL-2 on PC3 cell proliferation was analyzed. And the mechanism of rTCS was studied by western blot. After that the in vivo effect of rTCS combined with IL-2 was explored in mice bearing PC3 xenograft tumor.ResultsTrichosanthin was successfully expressed in BL21 and purified by 100 mM imidazole. It was shown to inhibit proliferation of PC3 cells in a dose-dependent manner with IC50 50.6 μg/ml. When combined with cytokine IL-2, a significant synergic effect was obtained. The inhibition rate on PC3 was around 50 % in combination group while only 35.5 % in single rTCS group at 50 μg/ml. Further, the expression of full length caspase-8 and Bcl-2 decreased significantly while cleaved caspase-8 and Bax were up-regulated, which suggest that caspase-8-mediated apoptosis pathway may be activated by rTCS in PC3 cells. Moreover, our data demonstrated that tumor volume and tumor weight were significantly reduced in rTCS-treated or rTCS/IL-2-treated nude mice bearing PC3 xenograft tumor compared with control. And significant difference was also found between rTCS and rTCS/IL-2 group.ConclusionsThis study demonstrates that rTCS is a potential agent with high in vitro and in vivo anti-tumor activity on PC3 cells. And rTCS combined with IL-2 is a promising strategy in treating patients with prostate cancer in future.

Human nasopharyngeal carcinoma can be radiosensitized by trichosanthin via inhibition of the PI3K pathway

“…Miao et al (4) reported that TCS successfully induced apop-4) reported that TCS successfully induced apop-) reported that TCS successfully induced apoptosis in glioma cells in a dose-and time-dependent manner by targeting leucine-rich repeat-containing G-protein coupled receptor 5 and downregulating the Wnt/β-catenin signaling pathway. It has also been reported that recombinant TCS inhibits the proliferation of PC3 cells in a dose-dependent manner in vitro, as well as significantly reducing prostate tumor weight and prostate tumor volume in vivo (2). In the present study, it was demonstrated that TCS potently radiosensitizes Recombinant TCS has been demonstrated to inhibit prostate cancer by activating the caspase-8-regulatory pathway to induce the apoptosis of PC3 cells (2).…”

“…Trichosanthin (TCS) is purified from the root tuber of Trichosanthes kirilowii (1). In China, TCS has been used historically as an abortifacient agent in early and midterm pregnancy and to treat invasive moles, ectopic pregnancies and hydatidiform moles (1,2). TCS is a typical type I ribosome-inactivating protein, which attacks eukaryotic cells ribosomes via its rRNA N-glycosidase activities (2).…”

“…In China, TCS has been used historically as an abortifacient agent in early and midterm pregnancy and to treat invasive moles, ectopic pregnancies and hydatidiform moles (1,2). TCS is a typical type I ribosome-inactivating protein, which attacks eukaryotic cells ribosomes via its rRNA N-glycosidase activities (2). In recent years, the biological and pharmacological activities of TCS have been investigated (1).…”

“…A previous study has reported that TCS may serve as a potential anticancer agent via suppressing the proliferation of various cancer cell types, including melanoma, colon carcinoma, lung cancer, stomach cancer, breast cancer, hepatoma and prostate cancer (3). TCS has been demonstrated to suppress the proliferation of HeLa cells by obstructing the protein kinase C/mitogen activated protein kinase signaling pathway and increasing cytosolic Ca 2+ concentrations (2,4,5). TCS also successfully reduced human choriocarcinoma cell proliferation by upregulating reactive oxygen species production (4).…”

TKP, a serine protease extracted from Trichosanthes kirilowii, inhibits the migration and invasion of colorectal adenocarcinoma cells by targeting Wnt/β‐catenin and Hedgehog/Gli1 signalings

“…Novelty, many biologically active ingredients of T. kirilowii were found to play important roles in lipid metabolism, anti‐inflammatory activity, and hypoglycemic activity (Iwabuchi, Kohno‐Murase, & Imamura, ; Shidoji & Ogawa, ). In addition, proteins extracted from T. kirilowii exert antitumor biological function (Li, Li, Zhang, Wang, & Zhang, ; Miao et al, ; Shaw, Lee, & Wong, ; Shi, Wong, & Shaw, ). TKP is a serine protease protein extracted from the fruit of T. kirilowii .…”