POTENTIAL ANTICANCER ACTIVITIES AND TOXICITIES OF TRITERPENE SAPONINE COMPOUNDS

Project no. 28468 · Status: Kapanmış (Yayın bekleniyor) · 2023

Summary

Cancer is a major global health threat and one of the leading causes of death worldwide. Over the past few decades, there is a constant need to discover new and effective anticancer drugs as it has become clear that cancer cells can acquire multidrug resistance to conventional anticancer drugs, causing tumor recurrence. Natural products derived from plants have served as the primary source of cancer drugs and continue to provide new plant-derived anticancer drugs. Triterpenes are naturally occurring alkenes of vegetable, animal, and fungal origin, called triterpenoids (Chudzik et al., 2015). Triterpene saponins are triterpenes that belong to the group of saponin compounds. Triterpene saponins are known as potential anticancer agents with different mechanisms of action. Their cytotoxic effects may be due to induction of apoptosis or stimulation of non-apoptotic cell death. Although many triterpene saponin compounds have been isolated to date, there is no study in the current literature on the anticancer, anti-angiogenic activity, and toxicity of these compounds. Therefore, this study, it was aimed to determine the antioxidant capacity of 3 triterpene saponin compounds (FA1, FA2, FA3) isolated from Astragalus L. and to reveal their cytotoxic, genotoxic, and anti-angiogenic effects. Within the scope of the study, In vitro Cell Based Antioxidant Capacity Determination test and MTT test to determine the in vitro cytotoxic effect of 3 triterpene saponin compounds, Flow Cytometry analysis to determine apoptosis, AMES test to determine genotoxic potential and evaluation of Cell Migration by In vitro Scratch Assay and HET-CAM test were performed to observe the angiogenic/antiangiogenic effect. When compared with control cells (cell viability 100%) and cells damaged with 1 mM H2O2 H2O2 (cell viability 30.1%), it was determined that FA1 did not show a protective effect against H2O2 damage at applied concentrations. It has been determined that FA2 has a protective antioxidant effect against H2O2 damage at all concentrations (25, 50, 75, and 100 µg/mL), and FA3 at 75 and 100 µg/mL. In the cytotoxicity test, the cytotoxic effect was observed only in FA1, and IC50 values were calculated for CCD34-LU, U87-MG, and SHSY-5Y cell lines. Apoptosis and necrosis were observed in flow cytometry analysis using the IC50 and the value of FA1. It was determined that all three compounds did not show genotoxic effects against Salmonella typhimurium TA98 and TA102 strains in +S9 and -S9 environments, even at maximum concentration (5000 µg/mL). The anti-angiogenic effect was observed with the HET-CAM test in the applications of FA1 at 400 µg/mL, FA2, and FA3 at 200 µg/mL and above. As a result, the biological activity and toxicity of these 3 triterpene saponin compounds have been demonstrated at the molecular level and it has been shown that these compounds can be potential anticancer agents. Further results should be supported by in vivo trials.

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