Antimetastatic activity of Sulforaphane.
The effect of Sulforaphane on the inhibition of lung metastasis induced by B16F-10 melanoma cells was studied in C57BL/6 mice by three different modalities of administration-simultaneous, prophylactic and after tumour developed. Of this simultaneous mode of Sulforaphane administration was found to be most effective. There was 95.5% inhibition of lung tumour nodule formation and 94.06% increase in the life span of metastatic tumour bearing animals. Highly elevated levels of lung hydroxyproline, lung uronic acid, lung hexosamine, serum sialic acid and serum gamma-glutamyl transpeptidase (GGT) in the metastatic control animals was found to be significantly lowered in the Sulforaphane treated animals. Histopathological analysis of lung tissues also correlated with these results. In the in vitro system Sulforaphane showed a significant inhibition in the invasion of B16F-10 melanoma cells across the collagen matrix. (3)H-thymidine proliferation assay showed that Sulforaphane could inhibit the proliferation of B16F-10 melanoma cells in vitro. Gelatin zymographic analysis showed that Sulforaphane could inhibit the activation of matrix metalloproteinases. These findings suggest that Sulforaphane reduced the invasion of B16F-10 melanoma cells by the inhibition of activation of matrix metalloproteinases, thereby inhibiting lung metastasis.
Thejass
P
P
Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala State 680555, India.
Kuttan
Girija
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001937:Brassica / Q000737:chemistry; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006595:Hexosamines / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D017879:Isothiocyanates; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D013454:Sulfoxides; D016019:Survival Analysis; D013778:Tetrazolium Salts; D013844:Thiazoles; D013861:Thiocyanates / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014574:Uronic Acids / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D006595:Hexosamines; D017879:Isothiocyanates; D013454:Sulfoxides; D013778:Tetrazolium Salts; D013844:Thiazoles; D013861:Thiocyanates; D014574:Uronic Acids; D003094:Collagen; D005723:gamma-Glutamyltransferase; C022616:thiazolyl blue; C016766:sulforaphane; D019158:N-Acetylneuraminic Acid; D006909:Hydroxyproline; D013936:Thymidine