Elimination of reactive oxygen speies formed by chemotherapeutic agent in imatinib resistant K562R cell line by sweetgum oil

Sweetgum Oil (SO) is a resinous exudate locally named " Sığla Yağı " obtained from the injured body of Liquidambar orientalis. Antibacterial, antioxidant, antiseptic and anti-inflammatory properties of SO have been reported in many studies. In this study, cytotoxic dose Tyrosine Kinase Inhibitors (TKI) and Sweetgum Oil combination was applied to cell lines in order to determine the differences on ROS formation in resistant K562R and sensitive K562S chronic myeloid leukemia cell lines and to observe the effects of ROS on autophagy. In K562R and K562S cell lines, the effects of the LC3α/β protein, which plays a role in the formation of autophagosomes, which are related to cytotoxicity, ROS formation, DNA damage, autophagy and autophagy, and the Atg4A protein, which becomes inactive due to ROS formation, on expression levels were examined. In cytotoxicity studies, the IC50 value of sweetgum oil in K562R cells was determined as 250 μg / ml and in K562S cells as 150 μg / ml. It was observed that the ROS formed by the use of sweetgum oil with H2DCFDA staining was 28.8% less in K562R cells compared to ponatinib and 23.8% less in K562S cells than imatinib. In combined applications, according to the single applications of sweetgum oil, it was observed that ROS decreased by 67.56% in K562R cells and 60.9% in K562S cells. 21.9% more ROS were observed in K562R cells than in K562S cells. Due to the ROS generated, more DNA damage occurred in cells treated with tyrosine kinase inhibitors than cells treated with sweetgum oil. It was observed by fluorescent microscope that sweetgum oil caused a decrease in autophagy activation in K562R cells and increased autophagy activation in K562S cells. In the Western blot experiment, it was observed that Atg4A expression was higher in cells treated with sweetgum oil, and Atg4A expression was decreased in other groups with high ROS. LC3-I expression decreased in K562R cells and increased in K562S cells when sweetgum oil was applied.