This study found an association between alterations in the TP53 gene and the synergy score for combination treatment with doxorubicin and an Src kinase inhibitor using human osteosarcoma cell lines (MG63 and U2OS) and human colon cancer cell line.
Three different reviewers, with varying experience of digital pathology and image analysis, applied an agreed QuPath scoring methodology to CD3 and p53 immunohistochemically stained TMAs from a colon cancer cohort (n = 661).
By array analysis, there were 17 significantly down-regulated and 7 significantly up-regulated miRNAs in subjects who later developed neoplasia. miR-215 was significantly up-regulated both 1-2 years prior to the onset of neoplasia (3.5-fold, <i>p</i> < 0.001) and 3-5 years prior to the onset of neoplasia (5.4-fold, <i>p</i> = 0.007). miR-215 expression was also increased in UC-associated colon cancers (5.3-fold, <i>p</i> = 0.03) and adjacent non-dysplastic UC tissue (6.2-fold, <i>p</i> = 0.02). p53 was expressed in 20% of patients prior to the onset of neoplasia and in 67% of UC-associated colon cancers, although was not correlated with miR-215 expression.
TRRAP silencing attenuated p53 accumulation in lymphoma and colon cancer models, whereas TRRAP overexpression increased mutp53 levels, suggesting a role for TRRAP across cancer entities and p53 mutations.
We also found that autophagy inhibition led to DENSpm-induced apoptosis through Atg5 down-regulation, p62 degradation and LC3 lipidation in both HCT116 and SW480 cells. p53 deficiency did not alter the response of the colon cancer cells to DENSpm-induced apoptotic cell death under autophagy suppression conditions.
To gain a more in-depth understanding of metabolic regulation by baseline levels of p53, we employed both metabolomics and transcriptomics analysis with human colon cancer cell-line HCT116 depleted of p53.
Results demonstrate that milimolar concentrations of butyrate has an anti-proliferative effect in all three colon cancer cell lines under study, leading to a decrease on cell viability, expression of P21, P53 and β-catenin, being able to modulate P-glycoprotein activity and to induce apoptosis by modulation of BAX/BCL-2 ratio.
The tumor suppressor protein p53 plays an important role in the development and progression of colon cancer, and the subcellular organelle localization directly affects its function.
Here, we have investigated ASAH1 expression at the protein level in human colon cancer cell lines and tissues from colon cancer patients, and have examined in vitro the possible link between ASAH1 expression and functional activity of p53 protein whose inactivation is associated with the progression from adenoma to malignant tumour in colon cancer.
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).
However, protein expression of p53 is not always universal, and additional methods may be required to assess p53 status in UC-associated colon cancers.
Therefore, the present study revealed that the loss of p53 expression levels in tumors was associated with aggressive clinicopathological characteristics in patients with colon cancer.
These agents co-induce p53 and NF-κB-dependent gene expression in cell lines from breast and colon cancer and in primary chronic lymphatic leukemia (CLL) cells.
Herein we report a new electrochemical method for early detection of p53 autoantibodies against colon cancer using a strategy that combines the strength of gold-loaded nanoporous iron oxide nanocube (Au@NPFe<sub>2</sub>O<sub>3</sub>NC)-based capture and purification while incorporating the inherent simplicity, inexpensive, and portable nature of the electrochemical and naked-eye colorimetric readouts.
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.
In this population-based cohort study, the interaction between p53 and 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGCR) expression, KRAS mutations, and the association between statin use and colon cancer survival was assessed.
Taken together, our results demonstrate that combination therapy with sulindac and vitamin C could be a novel anti-cancer therapeutic strategy for p53 wild type colon cancers.
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.
Knockdown of PHLDB3 more efficiently inhibits the growth of mouse xenograft tumours derived from human colon cancer HCT116 cells that contain wild type p53 compared with p53-deficient HCT116 cells, and also sensitizes tumour cells to doxorubicin and 5-Fluorouracil.