Activation of p38 Mitogen-Activated Protein Kinase during ent-11α-Hydroxy-16-kauren-15-one-Induced Apoptosis in Human Leukemia HL-60 Cells

Abstract

Kaurene-type diterpenes possess various biological activities including antitumor and anti-inflammatory effects. Indeed, we have found that an ent-kaurene diterpene, ent-11α-hydroxy-16-kauren-15-one (KD), induced apoptosis via caspase-8 activation in human promyelocytic leukemia HL-60 cells. However, the mechanism of caspase-8 activation by KD is not clear. In this study, we investigated the involvement of p38 mitogen-activated protein kinase (p38^MAPK) in KD-induced apoptosis. p38^MAPK was activated by treatment with KD parallel to DNA ladder formation. Pretreatment with SB203580, a specific inhibitor of p38^MAPK, attenuated induction of apoptosis by KD and inhibited activation of caspase-8. Cleavage of Bid, a typical substrate of caspase-8, was also inhibited by treatment with SB203580, suggesting that activation of p38^MAPK occurs upstream of caspase-8 during KD-induced apoptosis.

Abbreviations

KD:ent-11α-hydroxy-16-kauren-15-one

p38^MAPK:p38 mitogen-activated protein kinase

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