J 2004

Camptothecin induces autophagy of v-myb-transformed monoblasts

ŠMARDA, Jan, Eva ZAHRADNÍČKOVÁ, Karel SOUČEK and Viktor HORVÁTH

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

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
Změněno: 15/11/2006 13:00, prof. RNDr. Jan Šmarda, CSc.

Abstract

V originále

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.

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 project
Name: 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