Comparative analysis of curcumin in combination with CDK4/6 inhibitors, palbociclib and ribociclib on breast cancer cells

Breast cancer is the most common malignancy and mortality in the world and in our country. Although life expectancy is extended with existing chemotherapeutic agents, only 5-10% of patients live more than 5 years and developing drug resistance is the biggest problem in treatment. Therefore, it is necessary to investigate new agents and combinations and to elucidate the molecular mechanisms of these agents. The primary aim of this thesis study is to compare the possible synergistic cytotoxic effects of curcumin (KR) isolated from Curcuma longa plant with CDK4 / 6 inhibitors Palbociclib (PB) and Ribociclib (RB). The secondary aim is to determine through which type / types of death possible synergistic cytotoxic combinations to be detected. MTT method was used to measure cell viability. Calcusyn 2.1 program was used to determine the IC50 values and combination index values of the agents. An ELISA-based kit measuring DNA fragmentation was used for determination of apoptotic effects, and Autophagy Assay Kit, which specifically stains autophagic vacuoles for detection of autophagic cell death. It was determined that PB and RB decreased the viability of MCF-7 and MDA-MB-231 breast cancer cells depending on concentration and time and increased the amount of apoptosis (p <0.05). While KR decreased the viability of breast cancer cells depending on the concentration and time, it did not cause any significant change on the viability of the embryonic kidney cell line HEK-293 (p<0.05). The data obtained showed that when CDK 4/6 inhibitors were combined with KR, breast cancer cell viability was more inhibited than cells treated with PB or RB alone, and a significant increase in apoptotic effect occurred. These synergistic data shown for the first time in the literature revealed that KR, which does not have a cytotoxic effect on normal cells, can increase the cytotoxic effect of CDK 4/6 inhibitors.