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.
Highlights
Arsenic contamination in drinking well water is a serious public health problem in the world [1,2]
Basing on our previous result [40], we examined the effects of 3 mM arsenic on cellular invasion, a hallmark of malignancy grade of cancer cell and apoptosis, a marker for cell dead in cancer treatment
These results suggested that at this concentration, arsenic expressed its bidirectional functions in squamous cell carcinoma HSC5 cells
Summary
Arsenic contamination in drinking well water is a serious public health problem in the world [1,2]. Effects of arsenic as an agent for carcinogenesis or tumor progression or an anti-tumor drug depend on its concentration [4,5,6], duration of exposure [6,7] and cancer cell types [3,4,5,6,7]. Previous auto radiographic animal studies showed that cutaneous squamous cell carcinoma (SCC) is one of the representative arsenic-mediated cancers [8]. Arsenic expressed its anti-cancer effects on various solid cancers, including cutaneous carcinoma, through promoting apoptotic cell death [10,11]. There were many studies focusing on revealing the mechanism of effects of arsenic on cancer cells, it is still unclear
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