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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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N-cadherin and p21 transcript and protein expression levels in HSC5 cells treated with arsenic.A and C) transcript expression levels of N-cadherin and p21 were measured by real-time PCR. ***, significantly different (p<0.001) from the control by Student's t-test. B and D) Protein expression levels of N-cadherin and p21 were measured by immunoblot. TUBULIN was used as a positive control. Three independent experiments were performed and the same results were obtained.
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pone-0096945-g004: N-cadherin and p21 transcript and protein expression levels in HSC5 cells treated with arsenic.A and C) transcript expression levels of N-cadherin and p21 were measured by real-time PCR. ***, significantly different (p<0.001) from the control by Student's t-test. B and D) Protein expression levels of N-cadherin and p21 were measured by immunoblot. TUBULIN was used as a positive control. Three independent experiments were performed and the same results were obtained.

Mentions: We then investigated the molecular mechanism of arsenic-mediated apoptosis in HSC5 cells. Treatment with 3 µM of arsenic strongly reduced transcript and expression levels of N-cadherin (Figure 4A-B) and promoted transcript and expression levels of p21(WAF1/CIP1) (Figure 4C-D). Previous studies [20]–[24], [29]–[36] showed that N-cadherin and p21(WAF1/CIP1) might play important roles in modulating of apoptosis of human squamous cell carcinoma cells. Our results in this study suggested that arsenic might cause apoptosis of HSC5 cells through downregulation of N-cadherin and/or upregulation of p21(WAF1/CIP1).


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)

N-cadherin and p21 transcript and protein expression levels in HSC5 cells treated with arsenic.A and C) transcript expression levels of N-cadherin and p21 were measured by real-time PCR. ***, significantly different (p<0.001) from the control by Student's t-test. B and D) Protein expression levels of N-cadherin and p21 were measured by immunoblot. TUBULIN was used as a positive control. Three independent experiments were performed and the same results were obtained.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0096945-g004: N-cadherin and p21 transcript and protein expression levels in HSC5 cells treated with arsenic.A and C) transcript expression levels of N-cadherin and p21 were measured by real-time PCR. ***, significantly different (p<0.001) from the control by Student's t-test. B and D) Protein expression levels of N-cadherin and p21 were measured by immunoblot. TUBULIN was used as a positive control. Three independent experiments were performed and the same results were obtained.
Mentions: We then investigated the molecular mechanism of arsenic-mediated apoptosis in HSC5 cells. Treatment with 3 µM of arsenic strongly reduced transcript and expression levels of N-cadherin (Figure 4A-B) and promoted transcript and expression levels of p21(WAF1/CIP1) (Figure 4C-D). Previous studies [20]–[24], [29]–[36] showed that N-cadherin and p21(WAF1/CIP1) might play important roles in modulating of apoptosis of human squamous cell carcinoma cells. Our results in this study suggested that arsenic might cause apoptosis of HSC5 cells through downregulation of N-cadherin and/or upregulation of p21(WAF1/CIP1).

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