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

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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

ASJC Scopus subject areas

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

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    Thang, N. D., Yajima, I., Kumasaka, M. Y., Ohnuma, S., Yanagishita, T., Hayashi, R., Shekhar, H. U., Watanabe, D., & Kato, M. (2011). Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase. PLoS ONE, 6(10), [e25636]. https://doi.org/10.1371/journal.pone.0025636