2. Biochemical mechanisms underlying the pro-apoptotic activity of 7,8-dihydroxy-4-methylcoumarin in human leukemic cells

RIVEIRO ME, VAZQUEZ R, MOGLIONI A, GOMEZ N, BALDI A, DAVIO C, SHAYO C

BIOCHEMICAL PHARMACOLOGY

Año: 2008 vol. 75 p. 725 - 736

0006-2952

action, being necessary the elucidation of the mechanism of action with the understanding of the relationship between structure and activity. In the present study, we evaluated the pro-apoptotic activity of 7,8-dihydroxy-4-methylcoumarin (DHMC) and its underlying mechanisms in human leukemic cells. Here, we present evidence that DHMC induced selective and concentration-dependent apoptosis in human leukemic cells. The pro-apoptotic effect of DHMC was mediated by activation of the JNKs and inhibition of the ERK1/2 and PI3K/Akt pathways, with no participation of the p38 cascade after 24 h of treatment. Indeed, down-regulation of the proto-oncogene c-myc as well as induction of the cell cycle inhibitor p21WAF1/CIP1 through a p53 independent mechanism were observed in U-937 cells. These findings suggest that DHCM may have a potential therapeutic role in the future treatment of hematological malignancies.WAF1/CIP1 through a p53 independent mechanism were observed in U-937 cells. These findings suggest that DHCM may have a potential therapeutic role in the future treatment of hematological malignancies.