A sesquiterpene lactone, tomentosin, as a novel anticancer agent: orchestrating apoptosis, autophagy, and ER stress in colorectal cancer.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Natural compounds with anticancer potential, such as tomentosin, a sesquiterpene lactone derived from Inula viscosa, are under investigation as alternative therapeutic agents. However, its potential effects on CRC remain unexplored. This study aimed to evaluate the anticancer potential of tomentosin in CRC cells and elucidate its underlying molecular mechanisms. HCT 116 and HT- 29 cells were treated with tomentosin, and its effects on cell viability, colony formation, invasion, apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, autophagy, and endoplasmic reticulum (ER) stress were evaluated. Various assays, including XTT, colony formation, and Matrigel invasion assays, were used to assess cell viability, proliferation, and invasion. Tomentosin markedly reduced cell viability and colony formation in a dose-dependent manner. It suppressed invasion and induced apoptosis, as evidenced by an increased apoptotic index and upregulation of CASP3, CASP7, CASP8, CASP9, and BAX. Tomentosin disrupted MMP and elevated ROS levels, contributing to apoptotic signaling. Autophagic activity was significantly upregulated, with increased expression of BECLIN1, ATG5, ATG7, and MAP1LC3 A. ER stress markers GRP78, ATF6, CHOP, and XBP1 were also upregulated, suggesting a role in cell death. Tomentosin has anticancer effects in CRC cells by inducing apoptosis, modulating autophagy, and triggering ER stress. These findings underscore tomentosin's potential as a novel therapeutic candidate for CRC, warranting further in vivo and clinical investigations.