Lai Ying-Jiun, Lin Chien-I, Wang Chia-Lin, Chao Jui-I
Department and Institute of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan.
J Cell Biochem. 2014 Nov;115(11):1888-99. doi: 10.1002/jcb.24858.
Honokiol is a small biphenolic compound, which exerts antitumor activities; however, the precise mechanism of honokiol-induced apoptosis in the human colorectal cancer cells remains unclear. Here, we show that survivin and p53 display the opposite role on the regulation of honokiol-induced apoptosis in the human colorectal cancer cells. Honokiol induced the cell death and apoptosis in various colorectal cancer cell lines. Moreover, honokiol elicited the extrinsic death receptor pathway of DR5 and caspase 8 and the intrinsic pathway of caspase 9. The common intrinsic and extrinsic downstream targets of activated caspase 3 and PARP protein cleavage were induced by honokiol. Interestingly, honokiol reduced anti-apoptotic survivin protein and gene expression. Transfection with a green fluorescent protein (GFP)-survivin-expressed vector increased the colorectal cancer cell viability and resisted the honokiol-induced apoptosis. Meantime, honokiol increased total p53 and the phosphorylated p53 proteins at Ser15 and Ser46. The p53-wild type colorectal cancer cells were exhibited greater cytotoxicity, apoptosis and survivin reduction than the p53-null cancer cells after treatment with honokiol. Together, these findings demonstrate that the existence of survivin and p53 can modulate the honokiol-induced apoptosis in the human colorectal cancer cells.
厚朴酚是一种具有抗肿瘤活性的双酚类小分子化合物；然而，厚朴酚诱导人结肠癌细胞凋亡的确切机制仍不清楚。在此，我们表明生存素和p53在厚朴酚诱导人结肠癌细胞凋亡的调控中发挥相反作用。厚朴酚可诱导多种结肠癌细胞系发生细胞死亡和凋亡。此外，厚朴酚可引发DR5和半胱天冬酶8的外源性死亡受体途径以及半胱天冬酶9的内源性途径。厚朴酚可诱导激活的半胱天冬酶3和PARP蛋白裂解的常见内源性和外源性下游靶点。有趣的是，厚朴酚可降低抗凋亡生存素蛋白和基因表达。转染绿色荧光蛋白（GFP）-生存素表达载体可提高结肠癌细胞活力并抵抗厚朴酚诱导的凋亡。同时，厚朴酚可增加总p53以及丝氨酸15和丝氨酸46位点磷酸化的p53蛋白。用厚朴酚处理后，p53野生型结肠癌细胞比p53缺失型癌细胞表现出更大的细胞毒性、凋亡和生存素降低。总之，这些发现表明生存素和p53的存在可调节厚朴酚诱导的人结肠癌细胞凋亡。
