Camptothecin induces autophagy of v-myb-transformed monoblasts
| Authors | |
|---|---|
| Year of publication | 2004 |
| Type | Article in Periodical |
| Magazine / Source | Differentiation |
| MU Faculty or unit | |
| Citation | |
| Field | Genetics and molecular biology |
| Keywords | Myb; differentiation; programmed cell death; autophagy |
| Description | 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. |
| Related projects: |