Phytochemical analysis of <i>Artemisia kopetdaghensis</i>: Sesquiterpene lactones with proapoptotic activity against prostate cancer cells

Abstract

Phytochemical investigation of the aerial parts of Artemisia kopetdaghensis resulted in the isolation and charac-terization of three undescribed eudesmane-type sesquiterpene lactones, persianolide A, 4-epi-persianolide A, and 3 alpha,4-epoxypersianolide A, together with three previously described eudesmane-type sesquiterpene lactones, 11-epi-artapshin, 1 beta,8 alpha-dihydroxy-11 alpha,13-dihydrobalchanin, and 1 beta-hydroxy-11-epi-colartin. The abundantly obtained 11-epi-artapshin was oxidized to undescribed 11 alpha,13-dihydroeudesma-12,6 alpha-olide-1,8-dione and 8 beta-hy-droxy-11 alpha,13-dihydroeudesma-12,6 alpha-olide-1-one and acetylated to the undescribed 1,8-O-diacetyl-11 alpha,13-dihydroeudesma-12,6 alpha-olide. Structures were elucidated based on extensive spectral data analyses, including 1D and 2D NMR and HRESIMS. The absolute configuration was determined using calculated and experimental ECD spectral data. Compounds were subsequently subjected to the MTT assay to evaluate their cytotoxicity against prostate cancer cells (DU-145 and LNCaP). Related factors associated with the sequence of apoptosis were tested by ELISA, western blotting, and biochemical assay. Results suggested that 11-epi-artapshin hinders the growth of DU-145 cells through mitochondria-mediated apoptosis initiated by stimulation of ROS build-up, delta psi m depletion, regulation of the Bax/Bcl-2 ratio, and activation of caspase 3, respectively.