L-cysteine as a regulator for arsenic-mediated cancer-promoting and anti-cancer effects

Masashi Kato, Mayuko Y. Kumasaka, Kozue Takeda, Khaled Hossain, Machiko Iida, Ichiro Yajima, Yuji Goto, Nobutaka Ohgami

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Previous studies have shown that activities of tyrosine kinases and secretion of the active form of matrix metalloproteinase-2 (MMP-2) are correlated with promotion of tumor growth, while apoptotic cell death in cancer cells is correlated with anti-cancer effects. Although arsenic has been reported to have both cancer-promoting and anti-cancer effects, the mechanisms of the arsenic-mediated bidirectional effects remain unknown. We examined the effects of arsenic on both proto-oncogene c-RET-transfected NIH3T3 cells with benign characters and oncogenic RET-MEN2A-transfected NIH3T3 cells with malignant characters. Arsenic promoted not only c-RET tyrosine kinase activity but also genetically activated RET-MEN2A kinase activity with promotion of dimer formation of RET proteins. Arsenic also increased secretion of the active form of MMP-2 in both RET-MEN2A-transfectants and c-RET-transfectants. On the other hand, arsenic promoted poly-(ADP-ribose) polymerase (PARP) degradation and cell death in both malignant and non-malignant cells. Interestingly, l-cysteine inhibited the arsenic-mediated tumor-promoting effects (activation of kinases and MMP-2 secretion) but not arsenic-mediated anti-cancer effects (PARP degradation and cell death). Our results suggest redox-linked regulation of arsenic-mediated activities of kinases and MMP-2 secretion but not arsenic-mediated cell death. Our results also suggest that l-cysteine is an ideal supplement that inhibits arsenic-mediated tumor-promoting effects without affecting arsenic-mediated anti-cancer effects.

Original languageEnglish
Pages (from-to)623-629
Number of pages7
JournalToxicology in Vitro
Volume25
Issue number3
DOIs
Publication statusPublished - 2011 Apr 1
Externally publishedYes

Fingerprint

Arsenic
Cysteine
Matrix Metalloproteinase 2
Cell death
Tumors
Phosphotransferases
Poly(ADP-ribose) Polymerases
Protein-Tyrosine Kinases
Degradation
Dimers
Chemical activation
Cells

Keywords

  • Arsenic
  • Cancer
  • L-cysteine
  • RET tyrosine kinase

ASJC Scopus subject areas

  • Toxicology

Cite this

L-cysteine as a regulator for arsenic-mediated cancer-promoting and anti-cancer effects. / Kato, Masashi; Kumasaka, Mayuko Y.; Takeda, Kozue; Hossain, Khaled; Iida, Machiko; Yajima, Ichiro; Goto, Yuji; Ohgami, Nobutaka.

In: Toxicology in Vitro, Vol. 25, No. 3, 01.04.2011, p. 623-629.

Research output: Contribution to journalArticle

Kato, M, Kumasaka, MY, Takeda, K, Hossain, K, Iida, M, Yajima, I, Goto, Y & Ohgami, N 2011, 'L-cysteine as a regulator for arsenic-mediated cancer-promoting and anti-cancer effects', Toxicology in Vitro, vol. 25, no. 3, pp. 623-629. https://doi.org/10.1016/j.tiv.2010.12.012
Kato, Masashi ; Kumasaka, Mayuko Y. ; Takeda, Kozue ; Hossain, Khaled ; Iida, Machiko ; Yajima, Ichiro ; Goto, Yuji ; Ohgami, Nobutaka. / L-cysteine as a regulator for arsenic-mediated cancer-promoting and anti-cancer effects. In: Toxicology in Vitro. 2011 ; Vol. 25, No. 3. pp. 623-629.
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AB - Previous studies have shown that activities of tyrosine kinases and secretion of the active form of matrix metalloproteinase-2 (MMP-2) are correlated with promotion of tumor growth, while apoptotic cell death in cancer cells is correlated with anti-cancer effects. Although arsenic has been reported to have both cancer-promoting and anti-cancer effects, the mechanisms of the arsenic-mediated bidirectional effects remain unknown. We examined the effects of arsenic on both proto-oncogene c-RET-transfected NIH3T3 cells with benign characters and oncogenic RET-MEN2A-transfected NIH3T3 cells with malignant characters. Arsenic promoted not only c-RET tyrosine kinase activity but also genetically activated RET-MEN2A kinase activity with promotion of dimer formation of RET proteins. Arsenic also increased secretion of the active form of MMP-2 in both RET-MEN2A-transfectants and c-RET-transfectants. On the other hand, arsenic promoted poly-(ADP-ribose) polymerase (PARP) degradation and cell death in both malignant and non-malignant cells. Interestingly, l-cysteine inhibited the arsenic-mediated tumor-promoting effects (activation of kinases and MMP-2 secretion) but not arsenic-mediated anti-cancer effects (PARP degradation and cell death). Our results suggest redox-linked regulation of arsenic-mediated activities of kinases and MMP-2 secretion but not arsenic-mediated cell death. Our results also suggest that l-cysteine is an ideal supplement that inhibits arsenic-mediated tumor-promoting effects without affecting arsenic-mediated anti-cancer effects.

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