Exposure of the yeast Candida albicans to the anti-neoplastic agent adriamycin increases the tolerance to amphotericin B

J Pharm Pharmacol. 2003 Dec;55(12):1629-33. doi: 10.1211/0022357022359.

Abstract

Cancer patients experience a high incidence of fungal infections due to their immuno-suppressed condition. This work has investigated the interaction of an anti-neoplastic agent, adriamycin (doxorubicin), with the yeast Candida albicans and examined whether this drug altered the susceptibility of the yeast to amphotericin B - an anti-fungal agent used for the treatment of systemic fungal infections in cancer patients. Exposure to adriamycin for 24h increased the growth of C. albicans and increased the tolerance to amphotericin B by a small, but statistically significant, extent. Growth in adriamycin-supplemented medium suppressed the respiration rate of C. albicans, which resulted in a decrease in the ergosterol content of the fungal cell membrane. The tolerance to amphotericin B was lost after exposure to adriamycin for 48 h, which coincided with a restoration in the respiration rate and the ergosterol content of the fungal cell membrane. This work demonstrated that short-term exposure (24 h) to adriamycin increased the tolerance of C. albicans for amphotericin B, which may be mediated by a decrease in the ergosterol content as a result of an adriamycin-induced disruption of oxidative phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / pharmacology*
  • Antibiotics, Antineoplastic / pharmacology*
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • Candida albicans / growth & development
  • Candida albicans / metabolism
  • Doxorubicin / pharmacology*
  • Drug Interactions
  • Drug Tolerance
  • Ergosterol / metabolism

Substances

  • Antibiotics, Antineoplastic
  • Antifungal Agents
  • Amphotericin B
  • Doxorubicin
  • Ergosterol