Comparative proteomic profiling of MCF-7 breast cancer cells treated with doxorubicin.
Chan, Michelle Ching Ee.
Date of Issue2009
School of Chemical and Biomedical Engineering
Doxorubicin, an anthracycline antitumor drug, is widely used in the treatment of human breast cancer. While numerous studies have shown that doxorubicin is able to cause apoptosis, differentiation and growth arrest in cells, little is known about the associated effects doxorubicin has on the expression level of protein molecules. To understand the effect doxorubicin has on protein expression, we conducted a comparative proteomic analysis between MCF-7 breast cancer cells treated and untreated with doxorubicin to identify significant differentially expressed proteins. Exposure of MCF-7 cells to 0.1 μM of doxorubicin for 48 hours resulted in the identification of 32 proteins. The quantitation, identification and analysis of proteins are done using two-dimensional nano liquid chromatography/mass spectrometry separation and iTRAQ labeling technique. Based on comparative proteomic analysis, we suggest that doxorubicin may induce various anti-tumor activities in tumor cells simultaneously; it may enhance its role as a topoisomerase II inhibitor by up-regulating heat shock protein 90, induce up-regulation of histone 2A to repress transcription and while further studies are needed to illustrate this, the down-regulation of histone 2B may be involve in an apoptic pathway induced by doxorubicin’s role as an oxidizing agent. Taken together, it could be that including the use of HSP90-inhibitor drug in tandem with doxorubicin may improve the overall efficacy of treatment in cancer patients in the clinical setting.
Final Year Project (FYP)
Nanyang Technological University