Induction ofp53 andp21/WAF1/CIP1 expression by nitric oxide and their association with apoptosis in human cancer cells

Abstract

In this study, human and rat cancer cells were used to investigate the expression of p53 and p21/WAF1/CIP1 and their association with apoptosis after exposure to nitric oxide (NO). It was found that NO induced nuclear accumulation of p53 protein in a dose- and time-dependent manner. The level of p53 protein was elevated by about fivefold compared with that of mock-treated cells 48 h after exposure to 300 ppm NO. The induction of p53 by NO was found by pulse-chase analysis to be mainly regulated by post-translational modification. The correlation between p53 status and apoptosis induced by NO in human cancer cells was also investigated in this study. We found that apoptosis was easily induced in cells containing wild-type p53 (COLO 205 and Hep G2) after exposure to NO. The p21/WAF1/CIP1 protein was induced by NO in cells containing wild-type p53 (Hep G2) but not in cells without p53 (Hep 3B) or with mutated p53 (HT-29). Our results indicate that wild-type p53 and p21/WAF1/CIP1 expression was elevated in human cancer cells by exposure to NO and suggest that this may eventually promote apoptosis.

Induction of apoptosis by S-Nitrosoglutathione and Cu2+ or Ni2+ ion through modulation of bax, bad, and bcl-2 proteins in human colon adenocarcinoma cells

“…To investigate whether Cu 2 could modulate NO-induced apoptosis, the percentage of apoptotic cells was calculated by the TUNEL assay, which demonstrated that Cu 2 enhanced GSNOinduced apoptosis (Figure 3C). These results are consistent with those of our previous study that described how apoptosis is induced by NO in human cancer cells [5]. To demonstrate the critical role of Cu 2 in intracellular GSNO decomposition, HT 29 cells were pretreated with GSNO (1 mM) for 6 h, washed twice with PBS, and then treated with Cu 2 (2.5 mM) at the indicated times (Figure 4).…”

“…In this study, we con®rmed and extended our earlier ®ndings on the apoptotic effects of NO. The p53 and bax proteins were stimulated in NO-induced apoptosis, and, in contrast, expression of the bcl-2 gene was inhibited by NO [5,39]. Similar results were observed in previous studies that demonstrated that bcl-2 expression attenuates NO-induced apoptosis, caspase activation, and PARP cleavage in human cells [46±48].…”

The apple polyphenol phloretin inhibits breast cancer cell migration and proliferation via inhibition of signals by type 2 glucose transporter

“…These results are valuable for clinical applications. Similar results were also indicated in our previous papers indicated that in the colon cancer (HT 29, p53 His 273 mutated) cells the drugs which induced G0/G1 arrest were also detected [ 27 , 34 – 36 ].…”

Response of Primary Human Airway Epithelial Cells to Influenza Infection: A Quantitative Proteomic Study

“…A decoy database search strategy (NCBInr Homo sapiens with all protein sequences reversed) was also used to estimate the false discovery rate (FDR), defined as the percentage of reverse proteins identified against the total protein identification. For our data, the estimated FDR was 0.56%, which is low compared to other studies and indicates a very high reliability of the proteins identified …”