Natural killer cell activity and anti-tumour effects of dehydrocrotonin and its synthetic derivatives.
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.
Melo
Patricia S
PS
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), CP 6110, CEP 13083-970, Campinas, SP, Brazil. pmelo@unicamp.br
Justo
Giselle Z
GZ
Durán
Nelson
N
Haun
Marcela
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002470:Cell Survival / Q000187:drug effects; D029802:Croton / Q000737:chemistry; D045785:Diterpenes, Clerodane / Q000494:pharmacology*; D007107:Immune System / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D013778:Tetrazolium Salts; D013844:Thiazoles
D000972:Antineoplastic Agents, Phytogenic; D045785:Diterpenes, Clerodane; D013778:Tetrazolium Salts; D013844:Thiazoles; C103060:dehydrocrotonin; D010744:Phosphoric Monoester Hydrolases; C022616:thiazolyl blue