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

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.

• Authors: Nguyen Dinh Thang, Ichiro Yajima, Mayuko Y Kumasaka, Shoko Ohnuma, Takeshi Yanagishita, Rumiko Hayashi, Hossain U Shekhar, Daisuke Watanabe, Masashi Kato
• Journal: PloS one (PLoS One) Vol. 6 Issue 10 Pg. e25636 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 22022425 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Kinase Inhibitors
• Barium
• Protein-Tyrosine Kinases
• CSK Tyrosine-Protein Kinase
• Focal Adhesion Protein-Tyrosine Kinases
• src-Family Kinases
• CSK protein, human
• Extracellular Signal-Regulated MAP Kinases
• Matrix Metalloproteinase 14
• Arsenic

Topics

• Animals
• Arsenic (analysis, toxicity)
• Bangladesh
• Barium (analysis, toxicity)
• CSK Tyrosine-Protein Kinase
• Cell Adhesion (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Transformation, Neoplastic (pathology)
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibroblasts (drug effects, enzymology, pathology)
• Focal Adhesion Protein-Tyrosine Kinases (metabolism)
• Humans
• Keratinocytes (drug effects, enzymology, pathology)
• Matrix Metalloproteinase 14 (metabolism)
• Melanocytes (drug effects, enzymology, pathology)
• Mice
• NIH 3T3 Cells
• Protein Kinase Inhibitors (pharmacology)
• Protein-Tyrosine Kinases (antagonists & inhibitors, metabolism)
• Vietnam
• Water Pollution (analysis)
• Water Wells (chemistry)
• src-Family Kinases