Inhibitory effects of fusarochromanone on melanoma growth.
Fusarochromanone is a toxic metabolite produced by Fusarium equiseti, a fungus present in decaying cereal plants in northern latitudes; it has been detected in various food grains. Fusarochromanone has been shown to have both stimulatory and inhibitory effects on various mammalian cells, depending on the concentration used. Whether these cytotoxic effects can be used in the clinical treatment of tumors remains to be established. Here, we evaluated the effects of fusarochromanone on the growth of human melanoma cells both in vitro and in vivo. In vitro, low concentrations (0.1-1 nmol/l) of fusarochromanone were found to be cytotoxic to many melanoma cell lines. In contrast, growth of normal melanocytes was inhibited only at much higher fusarochromanone concentrations (100-200 nmol/l). In vivo, the growth of melanoma cells implanted subcutaneously in immuno-compromised mice was significantly (P<0.05) reduced by daily administration of fusarochromanone. Immunohistological analyses indicated a significant (P<0.05) increase in the expression of active caspase-3 in tumor masses of mice treated with fusarochromanone, compared with controls. Together, these observations show that fusarochromanone increased apoptosis of tumor cells and reduced tumor growth in vivo. Therefore, the effects of fusarochromanone warrant further investigation as an adjuvant molecule to prevent growth and recurrence of melanomas.
Department of Biology, University of North Carolina-Charlotte , Charlotte, North Carolina 28223, USA. ddreau@email.uncc.edu
Didier
D
Dréau
Mareva
M
Foster
Melanie
M
Hogg
Cathy
C
Culberson
Perla
P
Nunes
Roy E
RE
Wuthier
D000818:Animals; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D000970:Antineoplastic Agents; D002867:Chromones; D007202:Indicators and Reagents; D011500:Protein Synthesis Inhibitors; D053148:Caspase 3; C054523:fusarochromanone; D013936:Thymidine