Enhanced antitumour efficacy of ferulic acid nanoparticles in combination with doxorubicin - a promising strategy for breast cancer treatment

Abstract

Introduction: The discovery of anticancer drugs from natural plants represents a large interest around the world. Ferulic acid (FA) is a natural phenolic acid has antitumor activity. Doxorubicin (DOX) is a potent chemotherapeutic agent used in the treatment of breast cancer, but its clinical uses are limited due to its toxic effects. This study aimed to evaluate the antitumour effect of FA and its nanosuspension (FA-NS) alone and in combination with DOX in Ehrlich solid tumour (EST)-bearing mice. Material and methods: Thirty-five female mice were divided into 7 groups: control, EST, FA, FA-NS, DOX, FA + DOX, and FA-NS + DOX. Proliferation, autophagy, apoptosis, angiogenesis, oxidative stress, and total antioxidant capacity (TAC) were investigated. Results: Our results showed that FA alone or in combination with DOX decreased tumour weight, proliferation, and angiogenesis by downregulating AKT and vascular endothelial growth factor receptor 2 levels, with marked elevation in autophagy and apoptosis indicated by upregulating Beclin-1, LC3-II, and caspase-3 levels. In addition, reduction of oxidative stress was indicated by decreased malondialdehyde and elevated TAC levels. Interestingly, the combination treatment mitigates DOX-induced different toxicities through the reduction of high levels of troponin-1, creatine kinase-MB, alanine transaminase, aspartate transaminase, urea, and creatinine. Conclusions: The combination of FA with DOX has the ability not only to promote the antitumour activity of DOX but also to ameliorate the side effects of DOX with more significant results when the FA was formulated by the nanotechnology.