Cytotoxic and Apoptotic Effects of Flavonoids and a Geraniol Derivative from Artemisia kermanensis on Normal and Breast Cancer Cell Lines

Abstract

Background and objectives: The aim of this study was extraction, isolation, and identification of potent metabolites from aerial parts of Artemisia kermanensis Podl.“Dermaneh kermani’, the Iranian endemic species of Asteraceae family, and finally evaluation the anti-proliferative and apoptotic effects against normal and breast cancer cell lines. Methods: Air-dried aerial parts of A. kermanensis Podl. were extracted by maceration method with acetone/dichloromethane and then fractionated with MPLC apparatus using a gradient solvent system. The chemical structures of the isolated compounds were determined based on analysis of mass and nuclear magnetic resonance spectra. Anti-proliferative effects of the three compounds were determined by MTT assay against HUVEC, MDA-MB-231 and MCF-7 cells. The apoptotic effects of compounds 2 and 3 were determined by flow cytometry on MCF-7 cells. Results: Compound 1 (5,7-dihydroxy-3',4',6-trimethoxyflavone, eupatilin), compound 2 (5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone) and compound 3 (1-acetoxy-3,7-dimethyl-7-hydroxy-octa-2E,5E-dien-4-one) were isolated from the plant extract. Compound 3 was identified for the first time from A. kermanensis. Statistical studies revealed that this compound showed the most anti-proliferative properties on all three cell lines. In MCF-7 cells treated with concentration of 10 µg/mL of compound 3, 36% apoptosis was observed. Furthermore, compound 2 (5,7,3'-Trihydroxy-6,4',5'-trimethoxyflavone) showed 33% apoptosis at 650 µg/mL. Conclusion: In the present study, the cytotoxic and apoptotic effects of 5,7,3'-trihydroxy-6,4',5'-trimethoxyflavone and Compound 3 (1-acetoxy-3,7-dimethyl-7-hydroxy-octa-2E,5E-dien-4-one) were determined for the first time. On the other hand, since Compound 3 showed the most cytotoxic effects on the cancer cell lines, investigation of its biological effects is recommended.

Keywords

• apoptosis
• artemisia kermanensis
• breast cancer
• flavone
• geraniol derivative