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Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs
Institute of Animal Physiology and Genetics AS CR, v.v.i., 277 21 Libechov, Czech Republic
Institute of Microbiology AS CR, v.v.i., 142 20 Prague, Czech Republic
Laboratory of Experimental Medicine, Institute of Translational and Molecular Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital, 775 15 Olomouc, Czech Republic
Life Technologies, Frederick, MD 21704, USA
* Author to whom correspondence should be addressed.
Received: 31 August 2012; in revised form: 26 October 2012 / Accepted: 7 November 2012 / Published: 22 November 2012
Abstract: A comprehensive proteome map of T-lymphoblastic leukemia cells and its alterations after daunorubicin, doxorubicin and mitoxantrone treatments was monitored and evaluated either by paired comparison with relevant untreated control and using multivariate classification of treated and untreated samples. With the main focus on early time intervals when the influence of apoptosis is minimized, we found significantly different levels of proteins, which corresponded to 1%–2% of the total amount of protein spots detected. According to Gene Ontology classification of biological processes, the highest representation of identified proteins for all three drugs belong to metabolic processes of proteins and nucleic acids and cellular processes, mainly cytoskeleton organisation and ubiquitin-proteasome pathway. Importantly, we observed significant proportion of changes in proteins involved in the generation of precursor metabolites and energy typical for daunorubicin, transport proteins participating in response to doxorubicin and a group of proteins of immune system characterising response to mitoxantrone. Both a paired comparison and the multivariate evaluation of quantitative data revealed daunorubicin as a distinct member of the group of anthracycline/anthracenedione drugs. A combination of identified drug specific protein changes, which may help to explain anti-cancer activity, together with the benefit of blocking activation of adaptive cancer pathways, presents important approaches to improving treatment outcomes in cancer.
Keywords: anthracycline/anthracenedione; T-lymphoblastic leukemia; proteomics; early anti-cancer response; adaptive cancer mechanisms; protein biosynthesis; ubiquitin-proteasome system; energy metabolism; transport proteins; tumor immunity
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Tyleckova, J.; Hrabakova, R.; Mairychova, K.; Halada, P.; Radova, L.; Dzubak, P.; Hajduch, M.; Gadher, S.J.; Kovarova, H. Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs. Int. J. Mol. Sci. 2012, 13, 15536-15564.
Tyleckova J, Hrabakova R, Mairychova K, Halada P, Radova L, Dzubak P, Hajduch M, Gadher SJ, Kovarova H. Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs. International Journal of Molecular Sciences. 2012; 13(12):15536-15564.
Tyleckova, Jirina; Hrabakova, Rita; Mairychova, Katerina; Halada, Petr; Radova, Lenka; Dzubak, Petr; Hajduch, Marian; Gadher, Suresh J.; Kovarova, Hana. 2012. "Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs." Int. J. Mol. Sci. 13, no. 12: 15536-15564.