The effect of selected antineoplastic agents on the morphology of Candida albicans 5865

Abstract

When examined in an amino acid supplemented inorganic salts – glucose medium, the morphological development of Candida albicans 5865 is inhibited or delayed by several drugs common to cancer chemotherapy protocols. Yeast phase growth is inhibited by actinomycin D (100 μg/mL), bleomycin (500 μg/mL), 5-fluorouracil (1000 μg/mL), and hydroxyurea (1000 μg/mL). Germ tube formation was also inhibited by actinomycin D (100 μg/mL), and vincristine (100 μg/mL), doxorubicin and bleomycin (each at 500 μg/mL), and 5-fluorouracil, cyclohexamide, hydroxyurea, and vinblastine at 1000 μg/mL, respectively. Following a 3-h exposure to the above drugs supplemented with sublethal concentrations of amphotericin B (AMB), yeast germination and chlamydospore formation were delayed 60–96 h. Culturing yeasts for 24 h in the presence of both AMB and actinomycin D resulted in a 90% loss in viability. Two antimetabolites not common to chemotherapeutic protocols also showed fungistatic and fungicidal activity. At 24 h, pentamidine isethionate (100 μg/mL) alone had a 90% kill rate which increased to greater than 99.99% when combined with AMB. A cyclic hydroxaneic acid, 7-chloro-3,4-dihydro-1-hydroxycarbostyril (7-Cl ADHC), demonstrated the lowest minimum germ tube inhibitory concentration (1 μg/mL). A 90% kill rate was obtained after culturing yeasts for 24 h in 7-Cl ADHC (100 μg/mL) supplemented with AMB.

Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence ofCandidaandAspergillusspecies

“…These effects were potentiated when these drugs were combined with AMB; actinomycin D-AMB combinations resulted in 90% loss in cell viability. 23 In another study, at drug concentrations typically used during therapy, C. albicans isolates exposed to methotrexate but not cyclophosphamide, cytarabine or dacarbazine produced significantly higher amounts of catalase (a marker of oxitatative stress) than did unexposed isolates. 24 As catalase activity in Candida spp.…”

“…22,23 For example, both yeast-phase growth of and germ-tube formation by C. albicans were inhibited by treatment with actinomycin D, bleomycin, 5-FU and hydroxyurea at varying concentrations (100-1,000 μg/ml). 23 These effects were enhanced when the drugs were combined with AMB; in particular, actinomycin similar to the peak plasma concentrations of these agents that result from typical dosing; also, treatment with doxorubicin, vincristine and vinblastine inhibited Candida filamentation. These effects were potentiated when these drugs were combined with AMB; actinomycin D-AMB combinations resulted in 90% loss in cell viability.…”

Ribonucleotide reductases and their occurrence in microorganisms: A link to the RNA/DNA transition

“…An anaerobic RNR activity was not detectable [190]. Proliferation inhibition caused by hydroxyurea was observed in cultures of Wangiella dermatitidis [193], Candida albicans [194], Neurospora crassa [195,196] and Schizophyllum commune [197][198][199].…”

Mechanisms Potentiating Candida Infections. A Review

“…The direct effect of antineoplastic agents on C. albicans and other yeast was investigated by a number of workers. Land et al studied the effect of several antineoplastic agents on the morphology of C. albicans (58). They observed that germ tube formation was inhibited and forced into stasis by a number of these agents.…”