Caffeic acid, a dietary polyphenol, pre-sensitizes pancreatic ductal adenocarcinoma to chemotherapeutic drug

Abstract

Resistance to chemotherapeutics is an eminent cause that leads to search for options that help in diminution of pancreatic ductal adenocarcinoma (PDAC) by overcoming resistance issues. Caffeic acid (CFA), a polyphenol occurring in many dietary foods, is known to show antidiabetic and anticancer properties potential. To unveil the effect of CFA on PDAC, we carried out this research in PDAC cells, following which we checked the combination effect of CFA and chemotherapeutics and pre-sensitization effects of CFA. Multitudinous web-based approaches were applied for identifying CFA targets in PDAC and then getting their interconnections. Subsequently, we manifested CFA effects by in-vitro analysis showing IC50 concentrations of 37.37 and 15.06 µM on Panc-1 and Mia-PaCa-2, respectively. The combination index of CFA with different drugs was explored which showed the antagonistic effects of combination treatment leading to further investigation of the pre-sensitizing effects. CFA pre-sensitization reduced IC50 concentration of doxorubicin in both PDAC cell lines which also triggered ROS generation determined by 2′,7′-dichlorofluorescin diacetate assay. The differential gene expression analysis after CFA treatment showed discrete genes affected in both cells, i.e. N-Cad and Cas9 in Panc-1 and Pi3K/AkT/mTOR along with p53 in Mia-PaCa-2. Collectively, this study investigated the role of CFA as PDAC therapeutics and explored the mechanism in mitigating resistance of PDAC by sensitizing to chemotherapeutics. Communicated by Ramaswamy H. Sarma