Indium/Gallium Maltolate Effects on Human Breast Carcinoma Cells: In Vitro Investigation on Cytotoxicity and Synergism with Mitoxantrone

Abstract

In this study, we aimed to investigate in vitro whether the synthetized indium maltolate (InMal) and gallium maltolate (GaMal) could exert either a toxic effect toward breast cancer cell line MDA-MB-231 or an agonistic activity with mitoxantrone (MTX) in comparison to fibroblast cell line NIH-3T3. Both GaMal and InMal reduced viability of MDA-MB-231, and at a lesser extent of NIH3-T3, in a dose- and time-dependent mode, the outcome was more effective in comparison to MTX sole exposure. Both GaMal and InMal toxicity was reverted by iron citrate addition on NIH3-T3, not on MDA-MB-231, showing indirectly that gallium and indium’s mechanisms of action may include iron targeting. The agonistic activity against MDA-MB-231 survival was shown pretreating with 100 μM InMal for 24 h followed by medium exchange with MTX at 10 ng mL ^–1 or vice-versa but not with co-incubation of both compounds. In particular, InMal pretreating resulted more protective to MTX subsequent exposure.