Zinc Borate–Mediated Reduction of Lipid Droplets and Cooperative Suppression of Clonogenic Survival with mTOR Inhibition in Colorectal Cancer Cells

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, with progression and metastasis closely tied to metabolic adaptations, including lipid storage and utilization. Boron derivatives have been shown to influence lipid metabolism in animals and humans. Oral boric acid, for example, reduces body weight in mice by inducing thermogenic proteins in adipose and skeletal muscle, promoting lipolysis. In this study, the anticancer potential of zinc borate (ZnB) in CRC cell lines SW480 (primary) and SW620 (metastatic) by modulating lipid storage investigated. ZnB reduced cell viability in a dose-dependent manner, with SW620 cells showing greater resistance. Fluorescence imaging indicated decreased lipid droplet (LD)- containing cells, consistent with possible lipophagy involvement. Colony formation and wound healing assays revealed impaired proliferation and migration, further diminished by the autophagy inducer AZD-8055. Under glutamine-deprived conditions-known to enhance lipid storage and aggressiveness-combined ZnB and AZD-8055 treatment markedly reduced LD content, proliferation and motility. These results suggest that ZnB disrupts lipid homeostasis involved in CRC cell survival. Our findings highlight the potential therapeutic value of co-targeting lipid metabolism and autophagy to combat metabolically adaptive and aggressive CRC.