p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells.
Plant-derived natural polyphenols exhibit anticancer activity without showing any noticeable toxicities to normal cells. The aim of this study was to investigate the role of p53 on the anticancer effect of polyphenols isolated from Korean Artemisia annua L. (pKAL) in HCT116 human colorectal cancer cells. We confirmed that pKAL induced reactive oxygen species (ROS) production, propidium iodide (PI) uptake, nuclear structure change, and acidic vesicles in a p53-independent manner in p53-null HCT116 cells through fluorescence microscopy analysis of DCF/PI-, DAPI-, and AO-stained cells. The pKAL-induced anticancer effects were found to be significantly higher in p53-wild HCT116 cells than in p53-null by hematoxylin staining, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/PI-stained cells. In addition, expression of ectopic p53 in p53-null cells was upregulated by pKAL in both the nucleus and cytoplasm, increasing pKAL-induced cell death. Moreover, Western bot analysis revealed that pKAL-induced cell death was associated with upregulation of p53-dependent targets such as p21, Bax and DR5 and cleavage of PARP1 and lamin A/C in p53-wild HCT116 cells, but not in p53-null. Taken together, these results indicate that p53 plays an important role in enhancing the anticancer effects of pKAL by upregulating p53 downstream targets and inducing intracellular cell death processes.
['Jung|Eun Joo|EJ|', 'Lee|Won Sup|WS|0000-0003-0863-1424', 'Paramanantham|Anjugam|A|', 'Kim|Hye Jung|HJ|0000-0002-7067-6810', 'Shin|Sung Chul|SC|', 'Kim|Gon Sup|GS|0000-0002-0844-1009', 'Jung|Jin-Myung|JM|', 'Ryu|Chung Ho|CH|', 'Hong|Soon Chan|SC|', 'Chung|Ky Hyun|KH|', 'Kim|Choong Won|CW|']
D000970:Antineoplastic Agents D031172:Artemisia annua D016923:Cell Death D045325:HCT116 Cells D006801:Humans D034882:Lamins D000071137:Poly (ADP-Ribose) Polymerase-1 D059808:Polyphenols D059748:Proteolysis D016159:Tumor Suppressor Protein p53 D015854:Up-Regulation
p53 Artemisia annua L. cell death colorectal cancer polyphenols ROS acidic vesicles