Application of a New Heliomycin Derivative Against Breast Cancer Under Normoxia and Hypoxia

This study investigates the effects of heliomycin and its derivative LCTA-2614 on both hormone-dependent and hormone-independent breast cancer cell lines.Biological activity was assessed using the MTT assay, flow cytometry, and immunoblotting.Heliomycin exhibited potent antiproliferative activity across breast cancer cell lines of various molecular subtypes, with half-maximal inhibitory concentrations (IC 50 ) of 0.65 M in MCF7, 0.95 M in MDA-MB-231, and 0.79 M in HCC1954 cells.The water-soluble derivative LCTA-2614 showed comparable activity, with IC 50 values of 0.86 M in MCF7, 0.68 M in MDA-MB-231, and 0.60 M in HCC1954 cells.The compound LCTA-2614 demonstrated a more selective effect on tumor cells compared to heliomycin.Importantly, both compounds maintained their antiproliferative potency under hypoxic conditions, a known driver of chemoresistance.Additionally, compound LCTA-2614 induced apoptosis in hormonedependent MCF7 cells through a p53-associated pathways.These findings highlight heliomycin as promising molecular scaffolds for the development of new chemotherapeutic agents.Their retained activity under hypoxia suggests particular potential for the treatment of solid tumors with extensive hypoxic regions.