title: Bidirectional functions of arsenic as a carcinogen and an anti-cancer agent in human squamous cell carcinoma.
abstract: Bidirectional cancer-promoting and anti-cancer effects of arsenic for cancer cells have been revealed in previous studies. However, each of these effects (cancer-promoting or anti-cancer) was found in different cells at different treated-concentration of arsenic. In this study, we for the first time indicated that arsenic at concentration of 3 µM, equal to average concentration in drinking water in cancer-prone areas in Bangladesh, simultaneously expressed its bidirectional effects on human squamous cell carcinoma HSC5 cells with distinct pathways. Treatment with 3 µM of arsenic promoted cell invasion via upregulation of expression of MT1-MMP and downregulation of expression of p14ARF and simultaneously induced cell apoptosis through inhibition of expression of N-cadherin and increase of expression of p21(WAF1/CIP1) at both transcript and protein levels in HSC5 cells. We also showed that inhibition of MT1-MMP expression by NSC405020 resulted in decrease of arsenic-mediated invasion of HSC5 cells involving decrease in phosphorylated extracellular signal-regulated kinases (pERK). Taken together, our biological and biochemical findings suggested that arsenic expressed bidirectional effects as a carcinogen and an anti-cancer agent in human squamous cell carcinoma HSC5 cells with distinct pathways. Our results might play an important scientific evident for further studies to find out a better way in treatment of arsenic-induced cancers, especially in squamous cell carcinoma.
authors.affiliation: Department of Biochemistry and Plant Physiology, VNU University of Science, Vietnam National University, Hanoi, Vietnam.
authors.forename: Nguyen Dinh
authors.initials: ND
authors.lastname: Thang
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Aichi Prefecture, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yajima
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Aichi Prefecture, Japan.
authors.forename: Mayuko Y
authors.initials: MY
authors.lastname: Kumasaka
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Aichi Prefecture, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000494:pharmacology* / Q000633:toxicity*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology* / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D002273:Carcinogens; D050759:Cyclin-Dependent Kinase Inhibitor p21; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D025803:Tumor Suppressor Protein p14ARF; D053511:Matrix Metalloproteinase 14; D001151:Arsenic