Antiproliferative and Pro-apoptotic Effects of Sesquiterpene Lactones from <i>Schkuhria pinnata</i> in THP-1 Leukemia Cells

As <i>Schkuhria pinnata</i> is a food supplement commonly available on the European market, the aqueous-methanol extract from the aerial parts of <i>S. pinnata</i> was subjected to chromatographic separation to isolate compounds with antiproliferative and pro-apoptotic properties. This procedure led to the isolation of two previously undescribed sesquiterpene lactones (<b>1</b> and <b>2</b>) bearing an unusually modified germacranolide skeleton, four known heliangolides (<b>3</b>-<b>6</b>), together with flavonoids hispidulin and pectolinarigenin. The structures of isolated compounds were elucidated by a comprehensive analysis of HRMS and 1D and 2D NMR data. Sesquiterpene lactones (<b>1</b>-<b>6</b>) were evaluated for their antiproliferative activities in the THP-1, DU-145, and MCF-7 cancer cell lines. Compounds <b>3</b>-<b>6</b> showed an antiproliferative effect with the highest intensity in the THP-1 leukemic cell line. The most effective compound <b>5</b>, 2″-dehydroeucannabinolide semiacetal, induced apoptosis and loss of mitochondrial membrane potential, increased mitochondrial superoxide production, and suppressed mitochondrial ATP production in THP-1 cells.