Çetinkaya Sümeyra, Güçlü Ebru, Çınar Ayan İlknur, Vural Hasibe, Dursun Hatice Gül
Biotechnology Research Center, Field Crops Central Research Institute, Ankara, 06170, Türkiye.
Department of Basic Science and Health, Hemp Research Institute, Yozgat Bozok University, Yozgat, Türkiye.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 11. doi: 10.1007/s00210-025-04111-0.
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.
结直肠癌（CRC）仍是全球癌症相关死亡的主要原因。具有抗癌潜力的天然化合物，如从粘毛旋覆花中提取的倍半萜内酯托美汀，正作为替代治疗药物进行研究。然而，其对结直肠癌的潜在影响仍未得到探索。本研究旨在评估托美汀在结直肠癌细胞中的抗癌潜力，并阐明其潜在的分子机制。用托美汀处理HCT 116和HT - 29细胞，并评估其对细胞活力、集落形成、侵袭、凋亡、线粒体膜电位（MMP）、活性氧（ROS）产生、自噬和内质网（ER）应激的影响。采用包括XTT、集落形成和基质胶侵袭试验在内的各种试验来评估细胞活力、增殖和侵袭。托美汀以剂量依赖的方式显著降低细胞活力和集落形成。它抑制侵袭并诱导凋亡，凋亡指数增加以及CASP3、CASP7、CASP8、CASP9和BAX的上调证明了这一点。托美汀破坏MMP并提高ROS水平，促进凋亡信号传导。自噬活性显著上调，BECLIN1、ATG5、ATG7和MAP1LC3 A的表达增加。内质网应激标志物GRP78、ATF6、CHOP和XBP1也上调，表明其在细胞死亡中起作用。托美汀通过诱导凋亡、调节自噬和引发内质网应激在结直肠癌细胞中具有抗癌作用。这些发现强调了托美汀作为结直肠癌新型治疗候选药物的潜力，值得进一步进行体内和临床研究。
