Xiao Xiaoxue, Jian Yanbo, Jiang Yu, Wei Shudong, Song Wei
College of Life Science, Yangtze University, Jingzhou 434023, China; School of Life Science and Engineering, Henan University of Urban Construction, Pingdingshan 467036, China.
School of Clinical Medicine, Shandong Second Medical University, Weifang 261000, China.
Int J Biol Macromol. 2025 May;309(Pt 1):142635. doi: 10.1016/j.ijbiomac.2025.142635. Epub 2025 Mar 28.
Condensed tannins, natural antioxidants, are widely known for their antitumor activity with low toxicity. However, the antitumor mechanism of Salix babylonica leaf condensed tannins (SCTs) remains unclear. Here, we purified bioactive SCTs and analyzed their structural characteristics, antitumor effects on human ovarian cancer (OC) cells as well as related potential mechanism. FT-IR, ESI-MS, and HPLC analyses demonstrated that SCTs primarily consist of procyanidins with (epi)catechin as the main flavan-3-ol extension unit. SCTs significantly inhibited the proliferation and migration of OVCAR3 and A2780 cells, induced G0/G1 cell cycle arrest, and promoted apoptosis. SCTs induced apoptosis through the mitochondrial apoptotic pathway by decreasing mitochondrial membrane potential, increasing intracellular reactive oxygen species generation, elevating the Bax/Bcl-2 ratio, and activating caspase-3. Network pharmacology analysis speculated that SCTs exert anti-ovarian cancer effects by targeting multiple targets and pathways, among which the PI3K/AKT/ERK pathway may be the main pathway of action. Western blot confirmed that SCTs inhibited the phosphorylation of AKT, MEK, and ERK. Moreover, SCTs dose-dependently impaired OVCAR3 tumor spheroid growth in three-dimensional culture models. These results suggested that SCTs induced apoptosis in OC cells by activating the mitochondrial-associated apoptosis pathway and inhibiting the PI3K/AKT/ERK signaling pathway, showing potential as therapeutic agents for OC.
缩合单宁作为天然抗氧化剂，以其低毒性的抗肿瘤活性而广为人知。然而，垂柳叶缩合单宁（SCTs）的抗肿瘤机制仍不清楚。在此，我们纯化了具有生物活性的SCTs，并分析了它们的结构特征、对人卵巢癌（OC）细胞的抗肿瘤作用以及相关潜在机制。傅里叶变换红外光谱（FT-IR）、电喷雾电离质谱（ESI-MS）和高效液相色谱（HPLC）分析表明，SCTs主要由原花青素组成，以（表）儿茶素作为主要的黄烷-3-醇延伸单元。SCTs显著抑制了OVCAR3和A2780细胞的增殖和迁移，诱导G0/G1期细胞周期阻滞，并促进细胞凋亡。SCTs通过降低线粒体膜电位、增加细胞内活性氧生成、提高Bax/Bcl-2比值和激活半胱天冬酶-3，通过线粒体凋亡途径诱导细胞凋亡。网络药理学分析推测，SCTs通过靶向多个靶点和途径发挥抗卵巢癌作用，其中PI3K/AKT/ERK途径可能是主要作用途径。蛋白质免疫印迹法证实，SCTs抑制了AKT、MEK和ERK的磷酸化。此外，在三维培养模型中，SCTs以剂量依赖的方式损害了OVCAR3肿瘤球体的生长。这些结果表明，SCTs通过激活线粒体相关凋亡途径和抑制PI3K/AKT/ERK信号通路诱导OC细胞凋亡，显示出作为OC治疗药物的潜力。
