Superior antimitogenic and chemosensitization activities of the combination treatment of the histone deacetylase inhibitor apicidin and proteasome inhibitors on human colorectal cancer cells

摘要: Despite the effectiveness of histone deacetylase inhibitors, proteasome inhibitors and cytotoxic drugs on human cancers, none these types treatments by themselves has been sufficient to eradicate disease. The combination different modalities may hold enormous potential for eliciting therapeutic results. In current study, we examined effects treatment with inhibitor (HDACI) apicidin (APC) in colorectal cancer cells. molecular mechanisms combined their sensitize cells chemotherapies were also investigated. Cancer exposed agents alone combination, cell growth inhibition was determined MTT colony formation assays. HDAC, NF-κB activities as well reactive oxygen species (ROS) monitored. Cell cycle perturbation induction apoptosis assessed flow cytometry. expression cycle/apoptosis- cytoprotective/stress-related genes quantitative PCR EIA, respectively. potentiation sensitivity upon APC/PI studied. APC MG132, PI-1 or epoxomicin potently inhibited growth, disrupted cycle, induced apoptosis, decreased activity increased ROS production. These events accompanied altered associated cytoprotection/stress regulation. markedly enhanced chemosensitivity (50-3.7 x 10(4)-fold) a drug-, combination- subtype-dependent manner. results this study have implications development com-binatorial that include HDACIs, PIs conventional chemotherapeutic drugs, suggesting synergy general applicability various cancers.