Evaluation of Efficacy of Curcumin and Caffeic Acid Phenethyl Ester in Breast Cancer by Preclinical Studies

Abstract

Aims:: The aim of this study was to evaluate the combined and comparative efficacy of Caffeic acid phenethyl ester (CAPE) and curcumin in breast cancer. background: CAPE and curcumin are a class of phenolics. While curcumin is obtained from turmeric, CAPE is found in Baccharis sarothroides and Populus deltoides. Both agents are reported to produce activities in some cancer types. The combined and the comparative effects of two agents in breast cancer is not yet reported. objective: We evaluated the potential of CAPE and curcumin in both in vitro and in vivo breast cancer models. method: Human breast cancer cell lines, MDA-MB-231 and MCF-7 were exposed to CAPE and curcumin followed by functional assays such as cell cytotoxicity, cell proliferation and colony formation, cell cycle, mitochondrial membrane potential, apoptosis, and monodansylcadaverine (MDC) staining for autophagy. Computational analyses and mice model were also used. result: Employing computational analyses, both agents were found to exhibit drug like properties. Both molecules interacted with the key molecules of the NF-B pathway. CAPE and curcumin inhibited cell proliferation, colony formation, and invasion, and triggered apoptosis and autophagy in breast cancer cells. CAPE was found to be more effective in comparison to curcumin. Two agents working together were more effective than each agent working alone. Both agents suppressed the expression of survivin, Bcl-xL and GLUT-1. Further, cleaved PARP was increased by both agents. An induction in ROS generation was observed by both phenolics. Further, both molecules triggered a dissipation in mitochondrial membrane potential. In mice model implanted with Ehrlich-Lettre ascites carcinoma (EAC) cells, both drugs inhibited the growth of the tumour. The phenolics also modulated the metabolic parameters in tumour bearing mice. conclusion: The observations suggest that the combination of curcumin plus CAPE may be better in comparison to individual molecule. other: The study opens a window for analysing the efficacy of combination of CAPE and curcumin by more animal studies. This will provide a basis for examining the combined efficacy of two agents by clinical trial.