Indole-alkaloid–rich fraction of Ervatamia coronaria leaf extract regresses breast cancer by inducing apoptotic cell death

Abstract

Current anti-breast cancer therapies often cause severe toxicity to normal cells and promote chemoresistance, while their exorbitant costs limit their accessibility to many patients. This underscores the need for safer, effective, and affordable alternative treatment strategies. In this study, we evaluated the anti-breast cancer potential of an alkaloid-rich dichloromethane fraction of Ervatamia coronaria (DFE) leaf extract, identified by LC-MS to contain eight indole-alkaloids as its major constituents. Using 4T1 cell-induced tumour allografts in BALB/c mice, alongside cell-based assays including cell viability, scratch assay, immunoblotting, immunohistochemistry, and scanning electron microscopy, we investigated its mechanisms of action. DFE treatment induced cell cycle arrest in the sub-G1 phase, triggering apoptosis, with little effect on normal cells. Mechanistically, elevated mitochondrial ROS were identified as the primary driver of toxicity, as pre-treatment with NAC reversed DFE’s effects. Additionally, DFE downregulated AKT signalling in breast cancer cells. Importantly, DFE significantly reduced 4T1 tumour growth in vivo, both alone and in combination with doxorubicin, without exerting significant toxicity on healthy mice. These findings support further evaluation of DFE in clinical models.