Crocin-loaded liposomes sensitize MDA-MB 231 breast cancer cells to doxorubicin by inducing apoptosis

Abstract

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer with high heterogeneity and poor therapeutic responses to standard treatments. The use of herbal medicine for treatment of TNBC is gaining in popularity worldwide due to their better anti-tumor efficacy and less side effects compared to chemotherapy agents. Previous studies have shown that crocin, a natural carotenoid from saffron, induced cell apoptosis in a concentration-dependent behavior in TNBC MDA-MB-231 breast cancer cells. To improve anti-cancer properties of crocin, liposome-based formulation was prepared by the thin layer hydration-sonication method. The formulation was characterized based on particle size, zeta potential, morphology, encapsulation efficiency (EE) and cellular uptake. The formulation showed monodisperse distribution with an average size of 80 nm, about 70% EE and 11% loading capacity. The effect of crocin, and crocin-loaded liposomes in combination with doxorubicin (DOX) were evaluated using the MDA-MB-231 cell line. The results showed that crocin significantly increased the cytotoxicity of DOX, and crocin loaded liposome enhanced the cytotoxicity further. Flow cytometric analysis revealed that crocin loaded liposome in combination with DOX increased the number of cells in Sub-G1 and G2/M phases. Real time qPCR analysis showed that survivin, cyclin-B1, Bcl-xl mRNA were significantly down-regulated, while Bax and Bid mRNA levels were up-regulated following treatment with crocin loaded liposome compared to control. This study suggested that formulation of crocin into liposomes can be considered as a promising approach against tumor cells, especially when combining with the chemotherapy agent, DOX.