Antiproliferative and proapoptotic activities of a new class of pyrazole derivatives in HL-60 cells.
A series of N-substituted pyrazole derivatives have been synthesized and tested for their anticancer effect on the HL-60 leukaemia cell line. Four were active both in cell-growth inhibition and in inducing apoptosis. The inhibition of cell growth mainly reflects a compound-induced reduction in the number of cells in phases from S to M, whereas the induction of apoptosis involves inhibition of expression of Bcl-2 and enhanced expression of Bax with consequent reduced activation of the proapoptotic caspase 3. Finally, preliminary experiments carried out with tumor cells from myelogenous leukaemic patients showed that the compounds 4c, 4l, 4m, and 4n are indeed capable of inducing apoptosis.
Dipartimento di Scienze Farmaceutiche, Università di Genova, Viale Benedetto XV, 3, I-16132 Genova.
Maria
M
Anzaldi
Chiara
C
Macciò
Mauro
M
Mazzei
Maria
M
Bertolotto
Luciano
L
Ottonello
Franco
F
Dallegri
Alessandro
A
Balbi
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D008956:Models, Chemical; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D051028:bcl-2-Associated X Protein; D053148:Caspase 3