Role of Caveolin 1, E-Cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells

Abstract

Background: Methotrexate is one of the earliest cytotoxic drugs used in cancer therapy, and despite the isolation of multiple other folate antagonists, methotrexate maintains its significant role as a treatment for different types of cancer and other disorders. The usefulness of treatment with methotrexate is limited by the development of drug resistance, which may be acquired through different ways. To get insights into the mechanisms associated with drug resistance and sensitization we performed a functional analysis of genes deregulated in methotrexate resistant cells, either due to its co-amplification with the dhfr gene or as a result of a transcriptome screening using microarrays.

Urolithin A causes p21 up-regulation in prostate cancer cells

“…Data were processed by RMA (robust multi-array average) normalization in log2 base scale and using a baseline transformation to the median of control samples. Differentially expressed genes were obtained by applying a p value cutoff of less than 0.05, and a fold change of expression of at least twofold as described in Selga et al [24]. Normalized and raw data were submitted to the Gene Expression Omnibus database (GEO).…”

The Caveolin-1 Connection to Cell Death and Survival

“…In colon cancer cells, selection for methotrexate resistance is associated with increased Caveolin-1 expression [31,134]. Interestingly, in HT29 cells siRNA-mediated Caveolin-1 down-regulation reduces cell viability after metothrexate exposure [134].…”

CYP1A1 is overexpressed upon incubation of breast cancer cells with a polyphenolic cocoa extract

“…cDNA was synthesized in a total volume of 20 lL from RNA samples as described in Selga et al [24]. CYP1A1 and ERa mRNA levels were determined in an ABI Prism 7000 Sequence Detection System (Applied Biosystems) using 3 lL of the cDNA reaction and the assays-on-demand Hs00153120_m1 for CYP1A1, Hs01045818_m1 for ERa and Hs00356991_m1 for APRT (all from Applied Biosystems).…”