Abstract
Abstract Lung cancer is the leading cause of cancer-related death. The high prevalence coupled with the high death rate and current lack of effective therapy against this type of cancer have spurred research on the characteristics of tumor cells and the search for novel strategies to prevent and treat lung cancer. The relationship between the degree of heterogeneity of tumor cells vs. the tumor cells sensitivity to anti-cancer agents may reflect the presence of cancer causing stem cells. The H460 non-small cell lung cancer cell line has been documented to have a great degree of heterogeneity with various degrees of responsiveness to the anti-cancer drug paclitaxel. The objective of this investigation was to assess the phenotypic heterogeneity of the H460 cell line following treatment with CPI-613. CPI-613 is a novel anti-cancer agent that selectively targets the altered form of mitochondrial energy metabolism utilized by tumor cells, that illicit changes in mitochondrial enzyme activities and cellular redox status leading to apoptosis, necrosis, and/or autophagia of tumor cells, without affecting normal cells. Different populations of H460 cells were generated following treatment of these cells with 1-2 rounds of CPI-613. The IC50 for the sub-population of H460 cells was approximately twice higher than that of parent H460 population (52±8 vs. 29±3 μM), suggesting the H460 cell line have CPI-613-sensitive and less sensitive sub-populations. Gene expression profiling revealed a difference in the metabolic and signaling pathways altered by CPI-613 among the different sub-populations. The cellular morphology observed under the microscope and up-regulation of SNAI2 and mesenchymal markers suggested that the sub-population consisted of cells with the epithelial-mesenchymal transition (EMT) phenotype. Recent evidence suggests that cells that undergo EMT gain stem cell-like properties, thus giving rise to cancer stem cells. We were able to demonstrate that treatment of parent H460 cells with CPI-613 at 50 μM for 24 hrs eliminated the sensitive population and treatment for 48 hrs was able to completely eliminate the resistant population containing cells with stem cell-like properties. Citation Format: Candida N. Perera, Robert Rodriguez, Robert Shorr. Heterogeneous response of H460 non-small lung carcinoma cells to CPI-613, a novel compound that selectively alters tumor energy metabolism. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A65. doi:10.1158/1538-7445.CHTME14-A65
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have