Redox-proteomic analysis of doxorubicin resistance-induced altered thiol activity in uterine carcinoma

• Published in: Journal of pharmaceutical and biomedical analysis 2013-05, Vol.78-79, p.1-8
• Main Authors: Lin, Szu-Ting, Lo, Yi-Wen, Chang, Shing-Jyh, Wang, Wen-Ching, Chang, Margaret Dah-Tsyr, Lyu, Ping-Chiang, Chen, Yi-Wen, Chou, Hsiu-Chuan, Chan, Hong-Lin
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; carcinoma; cell cycle; Cell Line, Tumor; chemotherapy; cytoskeleton; DIGE; Doxorubicin; Doxorubicin - therapeutic use; drug resistance; Drug Resistance, Neoplasm; Female; gel electrophoresis; glycolysis; Humans; MALDI-TOF MS; matrix-assisted laser desorption-ionization mass spectrometry; Oxidation-Reduction; oxidative stress; proteins; Proteomics; rapid methods; Reactive Oxygen Species - metabolism; Redox-proteomics; Resistance; signal transduction; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sulfhydryl Compounds - metabolism; thiols; uterine neoplasms; Uterine Neoplasms - drug therapy; Uterine Neoplasms - metabolism
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2013.01.028

[Display omitted] ► Doxorubicin-induced drug resistance is one of the most serious obstacles in cancer chemotherapy. ► Cysteine-labeling based 2D-DIGE was employed to analyze redox regulation in uterine cancer. ► 33 unique protein features that were significantly changed in thiol reactivity were identified. ► The identified targets may contribute on the formation of drug resistance. Doxorubicin is an anticancer drug used in a wide range of cancer therapies; however, doxorubicin-induced drug resistance is one of the most serious obstacles of cancer chemotherapy. Recent studies have indicated that reduced oxidative stress levels in cancer cells induce drug resistance. However, the redox-modifications of resistance – associated cellular targets are largely unknown. Thus, the current study employed cysteine-labeling based two-dimensional differential gel electrophoresis (2D-DIGE) combined with MALDI-TOF mass spectrometry (MALDI-TOF MS) to analyze the effect of doxorubicin resistance on redox regulation in uterine cancer and showed 33 spots that were significantly changed in thiol reactivity. These proteins involve cytoskeleton regulation, signal transduction, redox-regulation, glycolysis, and cell-cycle regulation. The current work shows that the redox 2D-DIGE-based proteomic strategy provides a rapid method to study the molecular mechanisms of doxorubicin-induced drug resistance in uterine cancer. The identified targets may be used to further evaluate their roles in drug-resistance formation and for possible diagnostic or therapeutic applications.