Induction of apoptosis and inhibition of telomerase activity in human bone marrow and HL-60 p53 null cells treated with anti-cancer drugs.
Telomerase plays a key role in the maintenance of chromosomal stability in tumours, and the ability of anti-cancer agents to inhibit telomerase activity is under investigation. In this study, we evaluated the effect of etoposide and taxol, on the telomerase activity and telomere length in human leukaemia p53 null cells and human bone marrow cells, as well as apoptosis and cell cycle modulation. Results showed that after exposure to the drugs, HL-60 cells as well as the human progenitors underwent a block in G2 and subsequently apoptosis, whereas stromal cells from bone marrow did not undergo a block in G2 or enter apoptosis after etoposide exposure. Telomere length increased in stromal cells after treatment with both etoposide and taxol whereas in HL-60 cells only after etoposide treatment with. Bax, bcl-2 and bcl-x change their expression in stromal cells, whereas bcl-x was induced after drug treatment and bcl-2 down regulated in progenitor cells. Our data suggest that telomerase activity and apoptosis are correlated and they seem to be modulated by a common gene, bcl-2.
Malerba
I
I
Laboratory of Hematotoxicology-ECVAM, Institute for Health and Consumer Protection, Joint Research Centre-JRC, Ispra 21020 (VA), Italy.
Gribaldo
L
L
Diodovich
C
C
Carloni
M
M
Meschini
R
R
Bowe
G
G
Collotta
A
A
D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology*; D002453:Cell Cycle / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D019254:Genes, bcl-2 / Q000235:genetics; D018922:HL-60 Cells; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D015347:RNA Probes; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000187:drug effects / Q000648:ultrastructure; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D051028:bcl-2-Associated X Protein
D017304:Annexin A5; D000970:Antineoplastic Agents; C494826:BAX protein, human; D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D015347:RNA Probes; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D004247:DNA; D019098:Telomerase