Cyclooxygenase-2 and 5-lipoxygenase pathways in diosgenin-induced apoptosis in HT-29 and HCT-116 colon cancer cells.
We studied the relationship between diosgenin-induced apoptosis and arachidonic acid metabolism in two cancer cell lines, the HT-29 and HCT-116. Diosgenin is a steroidal saponin known for its antiproliferative and pro-apoptotic effects on cancer cells. We focused our attention on two enzymes intervening in two different pathways of arachidonic metabolism: cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX). HT-29 and HCT-116 cells express 5-LOX but only HT-29 cells express COX-2 since HCT-116 are deficient. After 40 microM diosgenin treatment, we observed apoptosis hallmarks in both cell lines but HT-29 cells were more resistant with delayed apoptosis. In these cells, COX-2 expression and activity were increased and for the first time we showed that diosgenin also increased 5-LOX expression and enhanced leukotriene B4 production. Inhibition of 5-LOX by AA-861 significantly reduced apoptosis in both cell lines but COX-2 inhibition by NS-398 strongly sensitized HT-29 cells to diosgenin-induced apoptosis compared to HCT-116 cells. In this study, we showed the implication of COX-2 and 5-LOX in diosgenin-induced apoptosis but these results demonstrate how difficult it is to assess the correlation between the apoptotic signalling pathway of diosgenin and arachidonic acid metabolism with certitude.
Lepage
Clemence
C
Université de Limoges, Institut GEIST, EA 4021, Biomolécules et thérapies anti-tumorales, Laboratoire de Biochimie, 87025 Limoges Cedex, France.
Liagre
Bertrand
B
Cook-Moreau
Jeanne
J
Pinon
Aline
A
Beneytout
Jean-Louis
JL
D017209:Apoptosis; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D016718:Arachidonic Acid / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004144:Diosgenin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007975:Leukotriene B4 / Q000737:chemistry; D009578:Nitrobenzenes / Q000494:pharmacology; D012503:Saponins / Q000494:pharmacology; D013256:Steroids / Q000737:chemistry; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D009578:Nitrobenzenes; D012503:Saponins; D013256:Steroids; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D007975:Leukotriene B4; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2; D053148:Caspase 3; D004144:Diosgenin