The investigation of the synergistic effects of a pan-aurora kinase inhibitor danusertib and caffeic acid phenethyl ester (CAPE) on pancreatic cancer cells

Pancreatic cancer is an extremely deadly type of cancer that often remains asymptomatic in its early stages, leading to diagnostic challenges and typically being diagnosed at advanced stages. These factors severely limit treatment options, and many studies are still underway to develop novel therapies. This study aims to elucidate the potential effects of the combination of CAPE and Danusertib on pancreatic cancer cells through cellular cycle and apoptotic mechanisms. In this study, the cytotoxicity, DNA cell cycle, and apoptotic effects of the combination of caffeic acid phenethyl ester (CAPE) and Pan-Aurora kinase inhibitor Danusertib were investigated on the CFPAC-1 pancreatic adenocarcinoma cell line. Cytotoxicity was assessed using the xCELLigence system, and the IC50 value for CAPE was found to be 6.37 µM. Subsequently, combination studies of CAPE and danusertib were conducted to form the CAPE IC50 6.37 µM+Danusertib 200 nM combination. In the DNA cell cycle analysis, CAPE IC50 did not have an effect on cell cycle when applied alone, while CAPE IC50 6.37 µM+Danusertib 200 nM combination revealed 79.57% for 24 hours, 63.65% for 48 hours G1 phase arrest. In the apoptosis analysis, treatment with CAPE IC50 by itself resulted in cells entering late apoptosis at rates of 67% for 24 hours and 65.34% for 48 hours. However, the combination of CAPE IC50 6.37 µM+Danusertib 200 nM led to cells entering early apoptosis at rates of 20.11% for 24 hours and 44.65% for 48 hours. In conclusion, it has been demonstrated through preclinical in vitro studies that the combination of CAPE IC50 6.37 µM+Danusertib 200 nM, which exhibits early apoptotic effects by arresting the cell cycle in the G1 phase, might be a potential to have significant implications in research on pancreatic cancer. These findings emphasize the potential of the combination of CAPE and Danusertib as a promising approach in the treatment of pancreatic cancer, providing guiding insights for advanced therapeutic strategies.