Amphotericin B Potentiation of the Cytotoxicity of Anticancer Agents Against Both Normal Hematopoietic and Leukemia Cells in Mice2

Abstract

Dose-response curves in AKR or CD2F1 mice were obtained for AKR leukemia, L1210 leukemia, and hematopoietic stem cells following in vivo administration of one of the following anticancer agents alone or in combination with amphotericin B (AmB): doxorubicin, lomustine, or melphalan. AmB potentiated drug cytotoxicity of all agents against both leukemias. Potentiation of all three agents was greatest with the AKR leukemia demonstrating dose-modifying factor (DMF) values of 1.8, 3.0, and 2.7, respectively, for lomustine, melphalan, and doxorubicin. L1210 leukemia was somewhat less sensitive to drug potentiation by AmB with respective DMF values of 1.8, 1.8, and 1.3. AmB did not potentiate the action of any agent against hematopoietic stem cells. The increased life-span assays generally confirmed the clonogenic assays supporting the validity of the latter results. The specificity of AmB potentiation of anticancer agent cytotoxicity for tumor cells indicates that AmB may be a useful addition to antitumor drug combinations.

Comparison of Structures and Cytotoxicity of Mupirocin and Batumin Against Melanoma and Several Other Cancer Cell Lines

“…Each conformation is characterized with a unique spatial organization of the chemical groups involving in non-covalent bonding. This structural plasticity creates a vast variety of bioactivities of these compounds, but makes the structureactivity relationship modelling rather difficult [13,42]. Moreover, a recent study reported a keto-enolic tautomerization of batumin that increases significantly the number of possible conformations of this compound [25].…”

Potentiation of the Antitumor Effect of Merocyanine 540‐mediated Photodynamic Therapy by Amifostine and Amphotericin B

“…It binds to ergosterols of fungal cell membranes and—with lower affinity—to sterols of mammalian plasma membranes (40–42). Amphotericin B forms discrete pores that make membranes permeable to ions and small molecules such as doxorubicin, cisplatin and carboplatin (43–49). Amphotericin B has been used successfully to overcome drug resistance in preclinical models of cancer (43–49).…”

“…Amphotericin B forms discrete pores that make membranes permeable to ions and small molecules such as doxorubicin, cisplatin and carboplatin (43–49). Amphotericin B has been used successfully to overcome drug resistance in preclinical models of cancer (43–49). The results of clinical trials, however, have been disappointing, with amphotericin B failing to reverse drug resistance in the majority of cases (50).…”

Drug Interactions Involving Antifungal Drugs: Time Course and Clinical Significance

“…Lastly, amphotericin has been demonstrated to enhance the intracellular penetration of anticancer agents into leukemic cells without affecting the penetration into normal hematopoietic stem cells in a number of in vitro models [1][2][3][4]. The time course and clinical significance of this phenomenon remains to be determined, so no clinical recommendations can be made at this time.…”