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Molecules 2016, 21(7), 934; doi:10.3390/molecules21070934

Protocatechualdehyde Induces S-Phase Arrest and Apoptosis by Stimulating the p27KIP1-Cyclin A/D1-CDK2 and Mitochondrial Apoptotic Pathways in HT-29 Cells

Sericultural Research Institute, Zhejiang Academy of Agricultural Science, Hangzhou 310021, China
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Academic Editor: Derek J. McPhee
Received: 18 June 2016 / Revised: 14 July 2016 / Accepted: 15 July 2016 / Published: 19 July 2016
(This article belongs to the Section Natural Products)
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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 p27KIP1 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 p27KIP1-mediated activation of the cyclin-A/D1-Cdk2 signaling pathway and the mitochondrial apoptotic pathway. View Full-Text
Keywords: Phellinus gilvus; protocatechualdehyde; S-phase arrest; apoptosis; HT-29 cells Phellinus gilvus; protocatechualdehyde; S-phase arrest; apoptosis; HT-29 cells
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MDPI and ACS Style

Zhong, S.; Li, Y.-G.; Ji, D.-F.; Lin, T.-B.; Lv, Z.-Q. Protocatechualdehyde Induces S-Phase Arrest and Apoptosis by Stimulating the p27KIP1-Cyclin A/D1-CDK2 and Mitochondrial Apoptotic Pathways in HT-29 Cells. Molecules 2016, 21, 934.

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