Antifungal activities of antineoplastic agents: Saccharomyces cerevisiae as a model system to study drug action.

Published

Journal Article (Review)

Recent evolutionary studies reveal that microorganisms including yeasts and fungi are more closely related to mammals than was previously appreciated. Possibly as a consequence, many natural-product toxins that have antimicrobial activity are also toxic to mammalian cells. While this makes it difficult to discover antifungal agents without toxic side effects, it also has enabled detailed studies of drug action in simple genetic model systems. We review here studies on the antifungal actions of antineoplasmic agents. Topics covered include the mechanisms of action of inhibitors of topoisomerases I and II; the immunosuppressants rapamycin, cyclosporin A, and FK506; the phosphatidylinositol 3-kinase inhibitor wortmannin; the angiogenesis inhibitors fumagillin and ovalicin; the HSP90 inhibitor geldanamycin; and agents that inhibit sphingolipid metabolism. In general, these natural products inhibit target proteins conserved from microorganisms to humans. These studies highlight the potential of microorganisms as screening tools to elucidate the mechanisms of action of novel pharmacological agents with unique effects against specific mammalian cell types, including neoplastic cells. In addition, this analysis suggests that antineoplastic agents and derivatives might find novel indications in the treatment of fungal infections, for which few agents are presently available, toxicity remains a serious concern, and drug resistance is emerging.

Full Text

Duke Authors

Cited Authors

  • Cardenas, ME; Cruz, MC; Del Poeta, M; Chung, N; Perfect, JR; Heitman, J

Published Date

  • October 1999

Published In

Volume / Issue

  • 12 / 4

Start / End Page

  • 583 - 611

PubMed ID

  • 10515904

Pubmed Central ID

  • 10515904

International Standard Serial Number (ISSN)

  • 0893-8512

Language

  • eng

Conference Location

  • United States