<b>Conclusions:</b> These results indicate that G9a-induced and p53-dependent epigenetic programing stimulates the growth of colon cancer, which also suggests that G9a inhibitors that restore p53 activity are promising therapeutic agents for treating colon cancer, especially for CRC expressing wild-type p53.
A recent study reported that a point mutation (G/T) in the p53 binding sequence in a colon cancer cell line completely impaired p53R2 protein activity.
According to Fearon and Vogelstein model, further somatic mutations in the K-ras oncogene, DCC gene and p53 tumor suppressor gene are prerequisite for development of colon carcinoma.
Also, the method was applied to the assay of p53 in human plasma sample and normal and malignant cell line lysates such as (L929 normal cell Line from mouse C3H (L929), colon cancer cell-HCT, prostate cancer cell line PC-3, and human breast adenocarcinoma cell line-MCF7).
Altogether, targeting BNIP3L in wild-type p53colon cancer cells is a novel anticancer strategy activating iron depletion signaling and the mitophagy-related cell death pathway.
Analytical scanning of the p53 gene by FAMA in DNA from colon cancer samples provides a sensitive, accurate and specific diagnostic procedure for routine clinical application.
Anti-proliferative activity was evaluated against the human colon carcinoma cell lines that had a normal expression of the p53 protein (HCT116 p53+/+) and mutants with a disabled TP53 gene (HCT116 p53-/-) and against the GM 07492 normal human fibroblast cell line.
As loss of p53 in colon cancer cells contributes to resistance against anticancer drugs, and thus to reoccurrence of colon cancer, targeted delivery of silica NPs could be envisioned to also deplete p53 deficient tumor cells.
By using pairs of isogenic colon cancer cell lines that differ only in p53 expression (RKO and HCT116), securinine was found to exhibit these properties.
Clonogenic survival analyses were performed using the human colon cancer cell lines HCT 116 wt and the isogenic p53 deficient cell line HCT 116 p53 -/-.
Collectively, our findings present the first to elucidate that miR-29c is a direct p53 target gene, and also identify PHLDB2 as an important miR-29c target gene involved in colon cancer metastasis.
Combined treatment with NVP-BEZ235 and curcumin reduced Bcl-2 expression in wild-type p53 HCT116 human colon carcinoma cells but not p53-null HCT116 cells.
Cytotoxicity assays showed that Adp14 had a statistically significantly (P =.002) greater effect on colon cancer (HCT116) cell lines containing two copies of the wild-type p53 gene than on p53-null cells, suggesting that functional p53 is a critical determinant of p14(ARF)-mediated cytotoxicity.
Data analysis comparing colon cancer entries in the TP53 database (http://p53.curie.fr) with the results reported in this study showed that distribution of mutations and the mutational events were comparable.
Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound.