# Antiproliferative and Pro-apoptotic Effects of Sesquiterpene Lactones from Schkuhria pinnata in THP‑1 Leukemia Cells

## TL;DR

This study identifies new compounds in Schkuhria pinnata that can stop leukemia cell growth and trigger cell death.

## Contribution

The discovery of two new sesquiterpene lactones with antiproliferative and pro-apoptotic effects in leukemia cells.

## Key findings

- Two new sesquiterpene lactones with a modified germacranolide skeleton were isolated from Schkuhria pinnata.
- Compound 5, 2″-dehydroeucannabinolide semiacetal, showed strong antiproliferative effects and induced apoptosis in THP-1 leukemia cells.
- The compound disrupted mitochondrial function, increasing superoxide production and reducing ATP synthesis in THP-1 cells.

## Abstract

As Schkuhria pinnata is a food supplement
commonly
available on the European market, the aqueous-methanol extract from
the aerial parts of S. pinnata 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 (1 and 2) bearing an unusually modified germacranolide skeleton, four known
heliangolides (3–6), 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 (1–6) were evaluated for their antiproliferative activities in
the THP-1, DU-145, and MCF-7 cancer cell lines. Compounds 3–6 showed an antiproliferative effect with the
highest intensity in the THP-1 leukemic cell line. The most effective
compound 5, 2″-dehydroeucannabinolide semiacetal,
induced apoptosis and loss of mitochondrial membrane potential, increased
mitochondrial superoxide production, and suppressed mitochondrial
ATP production in THP-1 cells.