Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase

Nguyen Dinh Thang, Ichiro Yajima, Mayuko Y. Kumasaka, Shoko Ohnuma, Takeshi Yanagishita, Rumiko Hayashi, Hossain U. Shekhar, Daisuke Watanabe, Masashi Kato

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl 2) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5-50 μM) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 μM) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5-5 μM) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro.

Original languageEnglish
Article numbere25636
JournalPLoS ONE
Volume6
Issue number10
DOIs
Publication statusPublished - 2011 Oct 12
Externally publishedYes

Fingerprint

barium
keratinocytes
Barium
phosphotransferases (kinases)
Phosphotransferases
Chemical activation
melanocytes
Arsenic
Fibroblasts
arsenic
drinking
neoplasms
fibroblasts
Water
Matrix Metalloproteinase 14
cell invasion
Keratinocytes
water
squamous cell carcinoma
melanoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase. / Thang, Nguyen Dinh; Yajima, Ichiro; Kumasaka, Mayuko Y.; Ohnuma, Shoko; Yanagishita, Takeshi; Hayashi, Rumiko; Shekhar, Hossain U.; Watanabe, Daisuke; Kato, Masashi.

In: PLoS ONE, Vol. 6, No. 10, e25636, 12.10.2011.

Research output: Contribution to journalArticle

Thang, ND, Yajima, I, Kumasaka, MY, Ohnuma, S, Yanagishita, T, Hayashi, R, Shekhar, HU, Watanabe, D & Kato, M 2011, 'Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase', PLoS ONE, vol. 6, no. 10, e25636. https://doi.org/10.1371/journal.pone.0025636
Thang, Nguyen Dinh ; Yajima, Ichiro ; Kumasaka, Mayuko Y. ; Ohnuma, Shoko ; Yanagishita, Takeshi ; Hayashi, Rumiko ; Shekhar, Hossain U. ; Watanabe, Daisuke ; Kato, Masashi. / Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase. In: PLoS ONE. 2011 ; Vol. 6, No. 10.
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