title: Arsenic trioxide inhibits HCCLM3 cells invasion through de novo ceramide synthesis and sphingomyelinase-induced ceramide production.
abstract: Arsenic trioxide (ATO) has shown anticancer activity against a variety of solid tumor models through induction of apoptosis, promotion of cellular differentiation, and inhibition of cellular invasive ability. The present study investigated the role of ceramide in regulating the invasive activity of hepatoma carcinoma HCCLM3 cells during ATO treatment. We found that ATO treatment inhibited HCCLM3 cell invasion and downregulated matrix metalloproteinase-9 (MMP-9) protein levels in a concentration-dependent manner. ATO also dose dependently induced the generation and accumulation of ceramide in HCCLM3 cells. Blockage of intracellular ceramide production through the inhibition of de novo ceramide synthesis or the hydrolysis of sphingomyelin increased the invasive ability and upregulated MMP-9 protein levels. The findings of this study indicated that ATO induced ceramide production through de novo ceramide synthesis and the hydrolysis of sphingomyelin and suggested that ceramide accumulation in response to ATO stimuli may play an important role in cancer therapy.
authors.affiliation: Department of General Surgery, The Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, People's Republic of China.
authors.forename: ShiHai
authors.initials: S
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: CuiLing
authors.initials: C
authors.lastname: Zhang
authors.forename: HuiWen
authors.initials: H
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: JianMin
authors.initials: J
authors.lastname: Bian
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: XiangYang
authors.initials: X
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002518:Ceramides / Q000096:biosynthesis*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D002518:Ceramides; D010087:Oxides; D013108:Sphingomyelin Phosphodiesterase; D020780:Matrix Metalloproteinase 9; D000077237:Arsenic Trioxide