Antitumor and immunomodulatory effect of coumarin and 7-hydroxycoumarin against Sarcoma 180 in mice.
The antitumor effect of peroral treatment with coumarin and its main metabolite in humans 7-hydroxycoumarin (7-OHC) against Sarcoma 180 in mice was studied. Both agents inhibited tumor growth and increased survival time of tumor-bearing animals. The antitumor effect was better when coumarins were administered prior to tumor inoculation suggesting that the immunomodulatory potential of coumarins might exceed their well-known direct cytostatic activity. The additive effect of coumarins in combination with a suboptimal LPS dose in tumor growth inhibition was demonstrated. Coumarin treatment enhanced the macrophage migration activity in the presence and absence of LPS and increased nitric oxide release. In vitro, coumarins induced IL-12 in murine macrophages and additively increased the LPS-induced IL-12 release. These data indicate that the immunomodulatory activity of coumarins contributes to their direct cytostatic effect and demonstrate their potential to combine as immunostimulators with other antitumor agents.
Stefanova
Tsvetanka H
TH
Dept. of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 26 Acad. G. Bonchev St., 1113 Sofia, Bulgaria.
Nikolova
Nadya J
NJ
Toshkova
Reneta A
RA
Neychev
Hristo O
HO
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000096:biosynthesis; D012510:Sarcoma 180 / Q000188:drug therapy*; D014468:Umbelliferones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D003374:Coumarins; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D014468:Umbelliferones; D018664:Interleukin-12; D009569:Nitric Oxide; C031477:7-hydroxycoumarin; C030123:coumarin