ŠMARDA, Jan, Eva ZAHRADNÍČKOVÁ, Karel SOUČEK and Viktor HORVÁTH. Camptothecin induces autophagy of v-myb-transformed monoblasts. Differentiation. Malden, MA 02148, USA: Blackwell Publishing, 2004, vol. 72, No 6, p. 279. ISSN 0301-4681.
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Basic information
Original name Camptothecin induces autophagy of v-myb-transformed monoblasts
Name in Czech Kamptotecin indukuje autofagii monoblastů transformovaných onkogenem v-myb
Authors ŠMARDA, Jan (203 Czech Republic, guarantor), Eva ZAHRADNÍČKOVÁ (203 Czech Republic), Karel SOUČEK (203 Czech Republic) and Viktor HORVÁTH (203 Czech Republic).
Edition Differentiation, Malden, MA 02148, USA, Blackwell Publishing, 2004, 0301-4681.
Other information
Original language English
Type of outcome Article in a journal
Field of Study Genetics and molecular biology
Country of publisher Germany
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 4.481
RIV identification code RIV/00216224:14310/04:00019786
Organization unit Faculty of Science
Keywords in English Myb; differentiation; programmed cell death; autophagy
Tags autophagy, differentiation, Myb, programmed cell death
Changed by Changed by: prof. RNDr. Jan Šmarda, CSc., učo 1223. Changed: 15/11/2006 13:00.
Abstract
Programmed cell death (PCD) pathways are frequently damaged during processes of malignant transformation. Abrogation of PCD can significantly affect the response of the cancer cell to a therapy. Therefore, understanding of molecular mechanisms regulating PCD in cancer cells is of potential clinical interest. In this study we analyzed PCD pathways in the cells of two leukemia cell lines: human U937 promonocytes and chicken v-myb-transformed BM2 monoblasts. PCD of these cells was induced using three agents: arsenic trioxide induces PCD by elevation of the intracellular level of hydrogen peroxide, cycloheximide acts as inhibitor of proteosynthesis and camptothecin inhibits activity of DNA topoisomerase I thus causing DNA damage. We found the mechanisms of PCD activated in BM2 and U937 cells by these agents partially different. Under conditions when U937 cells undergo caspase-mediated apoptosis, BM2 cells die by caspase-independent pathway. In addition, DNA damage caused by camptothecin results in a switch from apoptosis to autophagy in BM2 cells. Interestingly, camptothecin fails to induce similar effect in U937 cells. v-myb oncogene of avian myeloblastosis virus codes for regulator of proliferation, differentiation and apoptosis. Our results suggest that v-Myb oncoprotein over-expressed in BM2 but not in U937 cells can be significantly engaged in regulation of programmed cell death pathways in leukemic cells.
Abstract (in Czech)
V této práci jsme studovali dráhy programované buněčné smrti (PCD) v linii lidských promocytů (U937) a kuřecích monoblastů transformovaných v-myb (BM2). PCD těchto buněk byla idnukována třemi činidly: oxidem arsenitým, cykloheximidem a kamptotecinem. Zjistili jsme, že za podmínek, kdy buňky U937 odumírají apoptózou, buňky BM2 používají jinou dráhu PCD, která je nezávislá na kaspázách. Poškození DNA způsobené u buněk BM2 kamptotecinem, způsobuje autofagii. Naše výsledky dokazují onkoprotein v-Myb může být významně zapojen do procesů regulace PCD v leikemických bnkách.
Links
GA301/03/1055, research and development projectName: Studium molekulárních mechanismů způsobujících supresi v-Myb s využitím přístupů proteomiky
Investor: Czech Science Foundation, Study of molecular mechanisms causing v-Myb suppression using proteomics-based approach
MSM 143100008, plan (intention)Name: Genomy a jejich funkce
Investor: Ministry of Education, Youth and Sports of the CR, Genomes and their functions
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