title: Expression of survivin and p53 modulates honokiol-induced apoptosis in colorectal cancer cells.
abstract: 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.
authors.affiliation: Department and Institute of Biological Science and Technology, National Chiao Tung University, Hsinchu 30068, Taiwan.
authors.forename: Ying-Jiun
authors.initials: YJ
authors.lastname: Lai
authors.forename: Chien-I
authors.initials: CI
authors.lastname: Lin
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Wang
authors.forename: Jui-I
authors.initials: JI
authors.lastname: Chao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D001713:Biphenyl Compounds / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D045325:HCT116 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D051034:Inhibitor of Apoptosis Proteins; D017705:Lignans; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; C107489:BIRC5 protein, human; C495901:TP53 protein, human; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: APOPTOSIS; COLORECTAL CANCER; HONOKIOL; SURVIVIN; p53