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Induction of apoptosis by a stilbene analog involves bax translocation regulated by p38 MAPK and Akt

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Abstract

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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Authors and Affiliations

  1. College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea

    Kwang Sup So, Ji Eun Oh, Jee Hye Han, Hong Keun Jung, Young Suk Lee, Sang Hee Kim, Young Jin Chun & Mie Young Kim

  2. College of Pharmacy, Seoul National University, Seoul, Korea

    Sang Hee Kim

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  1. Kwang Sup So
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  2. Ji Eun Oh
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  3. Jee Hye Han
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Correspondence to Mie Young Kim.

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So, K.S., Oh, J.E., Han, J.H. et al. Induction of apoptosis by a stilbene analog involves bax translocation regulated by p38 MAPK and Akt. Arch. Pharm. Res. 31, 438–444 (2008). https://doi.org/10.1007/s12272-001-1176-7

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  • DOI: https://doi.org/10.1007/s12272-001-1176-7

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