title: Protocatechualdehyde Induces S-Phase Arrest and Apoptosis by Stimulating the p27(KIP1)-Cyclin A/D1-CDK2 and Mitochondrial Apoptotic Pathways in HT-29 Cells.
abstract: Protocatechualdehyde (PCA) extracted from Phellinus gilvus exhibits anti-cancer activity in human colorectal carcinoma cells (HT-29). However, the underlying mechanisms remain poorly understood. We performed an in vitro study involving MTT, flow cytometry, RT-PCR, and western blot analyses to investigate the effects of PCA treatment on cell proliferation, cell cycle distribution, apoptosis, and expression of several cell cycle-related genes in HT-29 cells. The treatment enhanced S-phase cell cycle and apoptosis in HT-29 cells in a dose-dependent manner. Western blot results showed that PCA treatment decreased the expression levels of cyclin A, cyclin D1, and p27(KIP1) but increased those of cyclin-dependent kinase 2 (CDK2) in HT-29 cells. Furthermore, the expression levels of B-cell lymphoma/leukemia-2 (Bcl-2) and B-cell lymphoma/leukemia-xL (Bcl-xL) were down-regulated, whereas the levels of BH3-interacting domain death agonist (Bid), Bcl-2 homologous antagonist/killer (Bak), and cytosolic cytochrome c were significantly upregulated. Thus, the enzymes caspases-9, -3, -8, and -6 were found to be activated in HT-29 cells with PCA treatment. These results indicate that PCA-induced S-phase cell cycle arrest and apoptosis involve p27(KIP1)-mediated activation of the cyclin-A/D1-Cdk2 signaling pathway and the mitochondrial apoptotic pathway.
authors.affiliation: Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China. zshi2002@163.com.
authors.forename: Shi
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China. liyougui3@163.com.
authors.forename: You-Gui
authors.initials: YG
authors.lastname: Li
authors.affiliation: Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China. dongfeng_ji@126.com.
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Ji
authors.affiliation: Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China. tianbao_lin@126.com.
authors.forename: Tian-Bao
authors.initials: TB
authors.lastname: Lin
authors.affiliation: Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China. lvzhiqiang_3@126.com.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Lv
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001547:Benzaldehydes / Q000737:chemistry / Q000494:pharmacology*; D002396:Catechols / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D056750:Cyclin A1 / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001547:Benzaldehydes; D002396:Catechols; D056750:Cyclin A1; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C005581:protocatechualdehyde; D051357:Cyclin-Dependent Kinase 2
keywords: HT-29 cells; Phellinus gilvus; S-phase arrest; apoptosis; protocatechualdehyde