The Molecular Mechanisms of Apoptosis Induced by A llium flavum L. and Synergistic Effects with New-Synthesized Pd(II) Complex on Colon Cancer Cells

Abstract

Considering that induction of apoptosis is one of the main strategies in cancer therapy, the molecular mechanisms of cytotoxic effects of Allium flavum L. on colon cancer cell lines were investigated and applied in single and co-treatments with new-synthesized Pd(II) complex. The analysis of chemical composition identified caffeic acid glycosides as the most dominant phenolics in A. flavum extract. In all investigated extracts, A. flavum showed cytotoxic effects on colon cancer cells (IC50 = 1.64–84 μg/mL) but not on healthy cells. Combinations of plant extracts with Pd(II) complex caused lower IC50 values and better proapoptotic activity. Pd(II) complex induced high percentage of necrosis in a single treatment, but in the combination with plant extracts it had better proapoptotic and lower necrotic activity. Treatments and co-treatments induced higher O2− production and influenced apoptosis biomarkers, leading to Fas protein overexpression and activation of caspases 8 and 9. Practical Applications In view of the achieved anticancer properties, insufficiently investigated Allium flavum L. is a promising candidate for developing new anticancer compounds and deserves further research and scientific validation. This study has great impact on investigation of new anticancer substances from natural source, focuses on the importance of using plants as the source of medicinal drugs, contributes to the development of the appropriate therapy and gives contribution in both scientific and practical means. Because of its synergistic actions with the newly synthesized chemical anticancer agent and ability to reduce side effects (thus reducing necrotic activity of Pd[II] complex), A. flavum can be used as a dietary food supplement or supplement to chemotherapy perhaps in combination with currently used chemotherapeutics or in some strategies in cancer therapy. This finding is also important from a nutritional point of view because this extracts contain significant amounts of bioactive constituents, which provide health benefits.