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• W2007754301 abstract "Betulinic acid and its derivatives are cytotoxic compounds with the specific effect to the tumor cells. In our betulinic acid derivative chemical library we have identified several potent compounds which were highly active in the wide spectrum of the cancer cell lines and the primary tumour cells as well as. Cell cycle modulating effects of selected compounds were monitored and surprisingly the compounds with different effect on the cell cycle profile were observed. Some derivatives were inhibiting the progression through the early S or G2-M phases and some were rapidly inducing the apoptosis. To identify the mechanisms of the action we have used genomic expressional (Affymetrix) and proteomic profiling (LC-MS/MS, SILAC). Derivatives inducing the rapid induction of the apoptosis were identified to regulate and affect the mRNA expression of the genes and proteins closely related to the oxidative stress and to the detoxification enzymes. Glutathione detoxification pathway and the oxidative phosphorylation cascade (upregulation of glutathion peroxidase, peroxiredoxine, thioredoxin, sulfiredoxine, cytochrome c oxidase, down regulation of glutathion S transferase) were affected and direct interaction of derivatives with cytochrome c was observed. All previously mentioned mechanisms are closely related to the mitochondrion damage. However, derivatives inducing the G2/M block were also increasing the expression of the tubulin chaperone cofactor A (TBCA) and the underexpression of other proteins like chaperonin containing TCP1, subunit 3 (CCT3) related to tubulin polymerization pathway and cell cycle regulation. Tubulin chaperone cofactors were recently suggested to be potential targets for the cancer therapy and current works are showing the upregulation of tubulin chaperone cofactor C correlated to the suppression of the tumor growth and increased chemosensitivity in resistant cancer phenotypes. This work was supported by the GACR 301/09/P433, GACR 305/09/1216 and CZ.1.05/2.1.00/01.0030). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2641. doi:10.1158/1538-7445.AM2011-2641" @default.
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• W2007754301 date "2011-04-15" @default.
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• W2007754301 title "Abstract 2641: Diversity of anticancer mechanisms of action of tritepenoids derived from betulinic acid" @default.
• W2007754301 doi "https://doi.org/10.1158/1538-7445.am2011-2641" @default.
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