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KMID : 0043320080310040438
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Archives of Pharmacal Research
2008 Volume.31 No. 4 p.438 ~ p.444
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Induction of Apoptosis by a Stilbene Analog Involves Bax Translocation Regulated by p38 MAPK and Akt
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So Kwang-Sup
Oh Ji-Eun
Han Jee-Hye
Jung Hong-Keun
Lee Young-Suk
Kim Sang-Hee
Chun Young-Jin
Kim Mie-Young
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Abstract
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trans-Stilbenes have been reported to induce cytochrome P450 1B1 (CYP1B1) inhibition and cell death, however, the molecular mechanisms of the effects are not fully understood. We report here that (1-(2-{3-[2-(2,4-dimethoxy-phenyl)-vinyl]-5-methoxy-phenoxy}ethyl)-1H-imidazole), a synthetic stilbene analog (SA) significantly suppressed TCDD-stimulated CYP1B1 mRNA expression. In HL-60 cells, SA induced apoptosis through activation of p38 MAPK and inactivation of Akt, which in turn activated Bad and mitochondrial death signaling pathway, as evidenced by Bax translocation and cytochrome c release. Expression of dominant negative p38 MAPK or constitutively active Akt significantly prevented cell death and mitochondrial Bax translocation, implicating that p38 MAPK and Akt signaling pathways play crucial roles in stilbene-induced apoptosis of HL-60 cells. These results suggest that SA induces apoptotic cell death as well as CYP1B1 inhibition and may thus be beneficial in cancer prevention.
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KEYWORD
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Stilbene, Apoptosis, p38 MAPK, Akt, Bax, Cytochrome P450 1B1
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