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

Thang ND, Yajima I, Kumasaka MY, Kato M - PLoS ONE (2014)

Bottom Line: However, each of these effects (cancer-promoting or anti-cancer) was found in different cells at different treated-concentration of arsenic.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Plant Physiology, VNU University of Science, Vietnam National University, Hanoi, Vietnam.

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.

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Related in: MedlinePlus

Effects of arsenic on invasive activity and phosphorylation and/or expression levels of MT1-MMP and ERK 4 in HSC5 cells.A), Invasive activity of HSC5 treated with 3 µM of arsenic was evaluated invasion assay. Level of invasive ability is presented as number of invading cells in a graph (left) and photographs (right). **, Significantly different (p<0.01) from the control by the Student's t-test. Phosphorylated levels of ERK (P-ERK) and protein expression levels of MT1-MMP and ERK in HSC5 cells treated with 3 µM arsenic for 24 hours are presented. TUBULIN protein expression levels are presented as an internal control.
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pone-0096945-g005: Effects of arsenic on invasive activity and phosphorylation and/or expression levels of MT1-MMP and ERK 4 in HSC5 cells.A), Invasive activity of HSC5 treated with 3 µM of arsenic was evaluated invasion assay. Level of invasive ability is presented as number of invading cells in a graph (left) and photographs (right). **, Significantly different (p<0.01) from the control by the Student's t-test. Phosphorylated levels of ERK (P-ERK) and protein expression levels of MT1-MMP and ERK in HSC5 cells treated with 3 µM arsenic for 24 hours are presented. TUBULIN protein expression levels are presented as an internal control.

Mentions: We next examined the effect of NSC405020, a MT1-MMP inhibitor, on arsenic-mediated invasion of HSC5 cells (Figure 5). Since MT1-MMP has been reported to be potential sited upstream of ERK [41], [42] and may be associated with arsenic-mediated invasion (Figure 2). Treatment with 3 µM arsenic again increased invasion (Figure 5A) with an increase in expression level of MT1-MMP (Figure 5B). However, there was no change in the phosphorylated level of ERK (pERK). These results indicated that the bidirectional effects of arsenic at this concentration on pERK were balance. Arsenic-mediated invasion was blocked by treatment with 1 µM of NSC405020 (Figure 5A). NSC405020 (1 µM) caused to decrease of expression level of MT1-MMP as well as decrease of phosphorylated of ERK in HSC5 cells (Figure 5B).


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

Thang ND, Yajima I, Kumasaka MY, Kato M - PLoS ONE (2014)

Effects of arsenic on invasive activity and phosphorylation and/or expression levels of MT1-MMP and ERK 4 in HSC5 cells.A), Invasive activity of HSC5 treated with 3 µM of arsenic was evaluated invasion assay. Level of invasive ability is presented as number of invading cells in a graph (left) and photographs (right). **, Significantly different (p<0.01) from the control by the Student's t-test. Phosphorylated levels of ERK (P-ERK) and protein expression levels of MT1-MMP and ERK in HSC5 cells treated with 3 µM arsenic for 24 hours are presented. TUBULIN protein expression levels are presented as an internal control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016145&req=5

pone-0096945-g005: Effects of arsenic on invasive activity and phosphorylation and/or expression levels of MT1-MMP and ERK 4 in HSC5 cells.A), Invasive activity of HSC5 treated with 3 µM of arsenic was evaluated invasion assay. Level of invasive ability is presented as number of invading cells in a graph (left) and photographs (right). **, Significantly different (p<0.01) from the control by the Student's t-test. Phosphorylated levels of ERK (P-ERK) and protein expression levels of MT1-MMP and ERK in HSC5 cells treated with 3 µM arsenic for 24 hours are presented. TUBULIN protein expression levels are presented as an internal control.
Mentions: We next examined the effect of NSC405020, a MT1-MMP inhibitor, on arsenic-mediated invasion of HSC5 cells (Figure 5). Since MT1-MMP has been reported to be potential sited upstream of ERK [41], [42] and may be associated with arsenic-mediated invasion (Figure 2). Treatment with 3 µM arsenic again increased invasion (Figure 5A) with an increase in expression level of MT1-MMP (Figure 5B). However, there was no change in the phosphorylated level of ERK (pERK). These results indicated that the bidirectional effects of arsenic at this concentration on pERK were balance. Arsenic-mediated invasion was blocked by treatment with 1 µM of NSC405020 (Figure 5A). NSC405020 (1 µM) caused to decrease of expression level of MT1-MMP as well as decrease of phosphorylated of ERK in HSC5 cells (Figure 5B).

Bottom Line: However, each of these effects (cancer-promoting or anti-cancer) was found in different cells at different treated-concentration of arsenic.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).

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Plant Physiology, VNU University of Science, Vietnam National University, Hanoi, Vietnam.

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.

Show MeSH
Related in: MedlinePlus