Pharmacological Properties and the Impact of Caffeic Acid-Entrapped Liposomes on Triple-Negative Breast Cancer Cell Lines Exposed to Doxorubicin

Background: Caffeic acid (CA), with antioxidant and immunomodulatory properties, was formulated in liposomes to increase its efficacy. The study targets triple-negative breast cancer (TNBC), characterized by the absence of ER, PR, and HER2 receptors. Methods: For CA-loaded liposomes, the pharmacological effects on TNBC cell lines, parental Hs578T (HS) and Doxorubicin-resistant Hs578T (HSD) cells were evaluated by determining the cell growth inhibition ratio measured by the (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, oxidative stress, apoptosis rate, membrane damage and transcription factor expressions, and DNA damage, with or without exposure to Doxorubicin (Dox). The Results: demonstrated that CA-loaded liposomes were stable and had high entrapment capacity. They exerted apoptotic effects on both cells, comparable to Doxorubicin, and increased cell membrane damage. The liposomes increased STAT3 expression in HS cells, while they reduced NRF2 and STAT3 in HSD cells, suggesting beneficial effects on Dox-resistant breast tumor cells. In HS cells exposed to Dox, CA treatment improved the number of viable tumor cells and decreased the rate of apoptosis, while in HSD cells it enhanced apoptosis as a mechanism of cell death and decreased pro-survival molecules, STAT3 expression in parallel with reduced NRF2 activation. Conclusions: The results indicated that CA encapsulated in liposomes was able to interfere with some survival mechanisms of triple-negative cells and could inhibit their proliferation.