Increase of Candida cell virulence by anticancer drugs and irradiation.
The influence of anticancer drugs and irradiation on Candida cell proliferation, adherence to HeLa cells and susceptibility to antifungal drugs (amphotericin B and miconazole) and neutrophils were examined using two Candida albicans strains. After treatment with 5-fluorouracil (25 microg/ml to 250 microg/ml), cis-diammine-dichloroplatinum (10 microg/ml to 100 microg/ml), peplomycin (0.5 microg/ml to 5 microg/ml) or 137Cs (20 Gy to 40 Gy) for 3 days or more, surviving Candida cells proliferated more rapidly than did untreated control cells. Anticancer agent-pretreated Candida cells revealed an increased adhesion to HeLa cells corresponding to an increase of binding to the lectins. The concentration of half limited colony formation (IC50) of amphotericin B and miconazole was increased to near two-fold that of the control by pretreatment of Candida cells with the anticancer agents, except peplomycin, which only weakly increased IC50. In addition, the enolase and Candida acid proteinase activities in the culture supernatants were increased by pretreatment with the drugs and irradiation. Correspondingly, surviving Candida cells after these treatments were resistant to neutrophils, with a reduction to half of the killing. These results indicate that anti-cancer drugs and irradiation potentiate the virulence of Candida cells, or they eliminate Candida cells with low virulence, thereby enhancing the risk of oral and systemic candidiasis.
Ueta
E
E
Department of Oral Surgery, Kochi Medical School, Kochi, Japan.
Tanida
T
T
Yoneda
K
K
Yamamoto
T
T
Osaki
T
T
D000666:Amphotericin B / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000187:drug effects / Q000528:radiation effects; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity* / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002588:Cesium Radioisotopes / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D005472:Fluorouracil / Q000494:pharmacology; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D037102:Lectins / Q000187:drug effects / Q000528:radiation effects; D008825:Miconazole / Q000494:pharmacology; D009504:Neutrophils / Q000382:microbiology; D017663:Peplomycin / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000187:drug effects / Q000528:radiation effects; D019275:Radiopharmaceuticals / Q000494:pharmacology*; D013223:Statistics as Topic; D014774:Virulence
D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D002588:Cesium Radioisotopes; D037102:Lectins; D019275:Radiopharmaceuticals; D017663:Peplomycin; D008825:Miconazole; D000666:Amphotericin B; D016282:Aspartic Acid Endopeptidases; D010751:Phosphopyruvate Hydratase; D002945:Cisplatin; D005472:Fluorouracil