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

• Published in: PloS one Vol. 6; no. 10; p. e25636
• Main Authors: Thang, Nguyen Dinh, Yajima, Ichiro, Kumasaka, Mayuko Y, Ohnuma, Shoko, Yanagishita, Takeshi, Hayashi, Rumiko, Shekhar, Hossain U, Watanabe, Daisuke, Kato, Masashi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.10.2011; Public Library of Science (PLoS)
• Subjects: Activation; Animals; Arsenic; Arsenic - analysis; Arsenic - toxicity; Bangladesh; Barium; Barium - analysis; Barium - toxicity; Bioaccumulation; Biological effects; Biology; Biomarkers; Breast cancer; Cancer; Cell Adhesion - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Transformation, Neoplastic - pathology; Dermatology; DNA damage; Drinking water; Environmental health; Enzyme Activation - drug effects; Enzyme inhibitors; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - enzymology; Fibroblasts - pathology; Focal adhesion kinase; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Growth; Health sciences; Humans; Keratinocytes; Keratinocytes - drug effects; Keratinocytes - enzymology; Keratinocytes - pathology; Kinases; Matrix Metalloproteinase 14 - metabolism; Medicine; Melanocytes; Melanocytes - drug effects; Melanocytes - enzymology; Melanocytes - pathology; Melanoma; Mice; NIH 3T3 Cells; Phosphatases; Phosphorylation; Protein expression; Protein Kinase Inhibitors - pharmacology; Protein phosphatase; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Proteins; Public health; Rodents; Skin; Skin cancer; Squamous cell carcinoma; Src protein; src-Family Kinases; Tumorigenesis; Vietnam; Water pollution; Water Pollution - analysis; Water Wells - chemistry; Well water; Young adults; Bangladesh; Vietnam; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0025636

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.