Down-modulation of Bcl-XL,release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells |
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Authors: | Yang Shu Er Hsieh Ming Tsuen Tsai Tung Hu Hsu Shih Lan |
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Affiliation: | Institute of Chinese Pharmaceutical Sciences, China Medical College, Taichung, Taiwan, ROC. |
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Abstract: | Honokiol is a phenolic compound purified from Magnolia officinalis, which induced the apoptotic cell death in several types of human cancer cells. In the present study, the molecular mechanism of honokiol-mediated apoptotic process was examined in human squamous lung cancer CH27 cells. Here, we found that honokiol-induced apoptotic cell death was accompanied by upregulation of Bad and downregulation of Bcl-XL, while honokiol had no effect on the levels of Bcl-2, Bcl-XS, Bag-1, Bax and Bak proteins. Moreover, honokiol treatment caused the release of mitochondrial cytochrome c to cytosol and sequential activation of caspases. Proteolytic activation of caspase-3 and cleavage of PARP, an in vivo substrate for caspase-3, were observed in honokiol-treated CH27 cells. Furthermore, treatment with caspase inhibitors z-DEVD-fmk and z-VAD-fmk markedly blocked honokiol-induced apoptosis. These results demonstrated that modulation of Bcl-XL and Bad proteins, release of mitochondrial cytochrome c and activation of caspase-3, participated in honokiol-triggered apoptotic process in human squamous lung cancer CH27 cells. |
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Keywords: | Adv, adenovirus DAPI, 4′,6-diamidino-2-phenylindole PARP, poly(ADP-ribose) polymerase TUNEL, terminal transferase-mediated dUTP-fluorescensin nick end-labeling YVAD-AFC, Tyr-Val-Ala-Asp-7-amino-4-trifluoromethyl coumarin VDVAD-AFC, Val-Asp-Val-Ala-Asp-7-amino-4-trifluoromethyl coumarin DEVD-AFC, Asp-Glu-Val-Asp-7-amino-4-trifluoromethyl coumarin VEID-AFC, Val-Glu-Ile-Asp-7-amino-4-trifluoromethyl coumarin IETD-AFC, Ile-Glu-Thr-Asp-7-amino-4-trifluoromethyl coumarin LEHD-AFC, Leu-Glu-His-Asp-7-amino-4-trifluoromethyl coumarin z-YVAD-fmk, z-Tyr-Val-Ala-Asp-fluoromethyl ketone z-DEVD-fmk, z-Asp-Glu-Val-Asp-fluoromethyl ketone z-VAD-fmk, z-Val-Ala-Asp-fluoromethyl ketone. |
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