Differential apoptosis by gallotannin in human colon cancer cells with distinct p53 status.

Gallotannin (GT), a plant polyphenol, has shown anticarcinogenic activities in several animal models including colon cancer. In our previous study, we showed that GT inhibits 1,2-dimethylhydrazine-induced colonic aberrant crypt foci and tumors in Balb/c mice, thus supporting a role for GT as a chemopreventive agent in colon cancer. However, at the molecular level, GT's mechanism of chemoprevention is still unclear. In this study, we aim at identifying GT's potential molecular mechanisms of action in in vitro studies. We show that GT differentially inhibits the growth of two isogenic HCT-116 (p53+/+, p53-/-) human colon cancer cells versus normal human intestinal epithelial cells (FHs 74Int). DNA flow cytometric analysis showed that GT induced S-phase arrest in both HCT-116 cell lines. Cell-cycle arrest in p53 (+/+) cells was associated with an increase in p53 protein levels and p21 transcript and protein levels. The inhibition of cell-cycle progression of HCT-116 p53 (+/+) cells by GT correlated with a reduction in the protein levels of cyclin D(1), pRb, and the Bax/Bcl-2 ratio. Although GT did not induce apoptosis in p53 (+/+) cells, a significant induction of apoptosis was observed in p53 (-/-) cells as shown by TUNEL staining and flow cytometry analysis. Apoptosis induction in p53 (-/-) cells was associated with a significant increase in Bax/Bcl-2 protein levels. Our results demonstrate that GT inhibits the growth of HCT-116 colon cancer cells in a p53-independent manner but exhibits differential sensitivity to apoptosis induction in HCT-116 cells with distinct p53 status.

Al-Ayyoubi S ，Gali-Muhtasib H 《MOLECULAR CARCINOGENESIS》

Onopordum cynarocephalum induces apoptosis and protects against 1,2 dimethylhydrazine-induced colon cancer.

El-Najjar N ，Saliba N ，Talhouk S ，Gali-Muhtasib H ... -  《ONCOLOGY REPORTS》

Enterolactone induces apoptosis and inhibits growth of Colo 201 human colon cancer cells both in vitro and in vivo.

Danbara N ，Yuri T ，Tsujita-Kyutoku M ，Tsukamoto R ，Uehara N ，Tsubura A ... -  《ANTICANCER RESEARCH》

Investigation of the role of Bax, p21/Waf1 and p53 as determinants of cellular responses in HCT116 colorectal cancer cells exposed to the novel cytotoxic ruthenium(II) organometallic agent, RM175.

Hayward RL ，Schornagel QC ，Tente R ，Macpherson JS ，Aird RE ，Guichard S ，Habtemariam A ，Sadler P ，Jodrell DI ... -  《CANCER CHEMOTHERAPY AND PHARMACOLOGY》

Adenovirus-mediated expression of p53 or p21 in a papillary serous endometrial carcinoma cell line (SPEC-2) results in both growth inhibition and apoptotic cell death: potential application of gene therapy to endometrial cancer.

Ramondetta L ，Mills GB ，Burke TW ，Wolf JK ... -  《CLINICAL CANCER RESEARCH》