Bidirectional functions of arsenic as a carcinogen and an anti-cancer agent in human squamous cell carcinoma

• Published in: PloS one Vol. 9; no. 5; p. e96945
• Main Authors: Thang, Nguyen Dinh, Yajima, Ichiro, Kumasaka, Mayuko Y, Kato, Masashi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09-05-2014; Public Library of Science (PLoS)
• Subjects: Anticancer properties; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Apoptosis; Apoptosis - drug effects; Arsenic; Arsenic - pharmacology; Arsenic - toxicity; Biological effects; Biology and Life Sciences; Cadherin; Cadherins; Cadherins - genetics; Cadherins - metabolism; Cancer; Cancer treatment; Carcinogens; Carcinogens - pharmacology; Carcinogens - toxicity; Carcinoma, Squamous Cell - pathology; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cip protein; Cyclin-dependent kinase inhibitor p21; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Dose-Response Relationship, Drug; Down-Regulation - drug effects; Drinking water; Drug therapy; GTP-binding protein; Humans; Inhibition; Kinases; Matrix Metalloproteinase 14 - genetics; Matrix Metalloproteinase 14 - metabolism; Matrix Metalloproteinase Inhibitors - pharmacology; N-Cadherin; Neoplasm Invasiveness; Pathways; RNA, Messenger - genetics; RNA, Messenger - metabolism; Skin cancer; Squamous cell carcinoma; Transcription; Tumor Suppressor Protein p14ARF - genetics; Tumor Suppressor Protein p14ARF - metabolism; Up-Regulation - drug effects; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096945

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.