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Arecoline-induced growth arrest and p21WAF1 expression are dependent on p53 in rat hepatocytes by Wen-Wen Chou; Jinn-Yuh Guh; Jung-Fa Tsai; Chi-Ching Hwang; Hung-Chun Chen; Jau-Shyang Huang; Yu-Lin Yang; Wen-Chun Hung; Lea-Yea Chuang is a Environmental Science article available to read on EtoBox.

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Betel-quid use is associated with the risk of liver cirrhosis and hepatocellular carcinoma and arecoline, the major alkaloid of betel-quid, is hepatotoxic in mice. Therefore, we studied the cytotoxic and genotoxic effects of arecoline in normal rat hepatocytes (Clone-9 cells). Arecoline dose-dependently (0.1-1 mM) decreased cell cycle-dependent proliferation while inducing DNA damage at 24 h. Moreover, arecoline (1 mM)-induced apoptosis and necrosis at 24 h. Arecoline dose-dependently (0.1-0.5 mM) increased transforming growth factor-␤ (TGF-␤) mRNA, gene transcription and bioactivity and neutralizing TGF-␤ antibody attenuated arecoline (0.5 mM)-inhibited cell proliferation at 24 h. Arecoline (0.5 mM) also increased p21 WAF1 protein expression and p21 WAF1 gene transcription. Moreover, arecoline (0.5 mM) time-dependently (8-24 h) increased p53 serine 15 phosphorylation. Pifithrin-␣ (p53 inhibitor) and the loss of the two p53-binding elements in the p21 WAF1 gene promoter attenuated arecoline-induced p21 WAF1 gene transcription at 24 h. Pifithrin-␣ also attenuated arecoline (0.5 mM)-inhibited cell proliferation at 24 h. We concluded that arecoline induces cytotoxicity, DNA damage, G

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Author

Wen-Wen Chou; Jinn-Yuh Guh; Jung-Fa Tsai; Chi-Ching Hwang; Hung-Chun Chen; Jau-Shyang Huang; Yu-Lin Yang; Wen-Chun Hung; Lea-Yea Chuang

Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 0300-483X)

Published

2008

Language

EN

Field

Environmental Science (Life Sciences)