Natural killer cell activity and anti-tumour effects of dehydrocrotonin and its synthetic derivatives

Abstract

In this work, the anti-tumour properties of dehydrocrotonin and its derivatives were investigated in vitro and in vivo using the Ehrlich ascites tumour model. Treatment of Ehrlich ascites tumour-bearing mice with 20 mg/kg dehydrocrotonin for 4 days significantly increased survival, whereas administration of dehydrocrotonin derivatives was ineffective in affording protection. Compound IV exhibited little activity against Ehrlich tumour cells in vitro. Investigation of the effects of dehydrocrotonin treatment on total natural killer (NK) cell activity of tumour-bearing mice as a possible mechanism of dehydrocrotonin action in vivo revealed that this sesquiterpene lactone significantly improved NK cytotoxicity against YAC-1, a Moloney virus-induced mouse T-cell lymphoma of A/SN origin. As expected, tumour growth in non-treated mice markedly suppressed NK cell cytolysis. No effects on NK functional activity were observed in normal mice receiving dehydrocrotonin. In summary, only the natural compound exhibits anti-tumour efficacy and immunomodulatory actions in vivo, which may be related to its chemical structure. (C) 2004 Elsevier B.V. All rights reserved.