Abstract：Objective: To explore the mechanism of mitochondrial damage induced by Hedyotis diffusa ethanol in cervical cancer cells, with a focus on clarifying the key role of ULK1 activation in this process. Methods: Cell culture, CCK-8 assay, flow cytometry, Western blot, and other techniques were employed to detect cervical cancer cells treated with Hedyotis diffusa ethanol, including cell proliferation, apoptosis, mitochondrial function, and the expression and activation of ULK1. Additionally, a cervical cancer xenograft tumor model was constructed to study the effects of Hedyotis diffusa ethanol on the growth of xenograft tumors, the expression of related proteins in tumor tissues, histopathology, and serum biochemical indicators in nude mice. Results: Hedyotis diffusa ethanol effectively inhibited the proliferation of cervical cancer cells, induced apoptosis, reduced mitochondrial membrane potential, increased reactive oxygen species production, and promoted ULK1 activation. Specifically, the inhibition rate of cell viability increased significantly with increasing Hedyotis diffusa ethanol concentration and treatment time; the apoptosis rate increased with increasing drug concentration (P<0.01); the proportion of cells with decreased mitochondrial membrane potential and increased reactive oxygen species levels increased with increasing drug concentration (P<0.01); the expression levels of ULK1, p-ULK1, LC3/LC3I, and Bax proteins increased with increasing drug concentration, while the expression level of Bcl-2 protein decreased (P<0.01). In animal experiments, the tumor volume in each Hedyotis diffusa ethanol dose group was significantly reduced, and the tumor inhibition rate increased with the dose; compared with the model group, the expression levels of ULK1, p-ULK1, LC3II/LC3I, and Bax proteins increased, while the expression level of Bcl-2 protein decreased (P<0.01); tumor cell necrosis increased, and the disorder of cell arrangement was alleviated; the content of MDA in serum decreased, and the activity of SOD increased (P<0.01). Conclusion: Hedyotis diffusa ethanol may induce mitochondrial damage in cervical cancer cells by activating ULK1, thereby exerting an anticancer effect. This study provides a theoretical basis for the application of Hedyotis diffusa ethanol in the treatment of cervical cancer, but the specific molecular mechanism between ULK1 activation and mitochondrial damage requires further investigation.
段佳奇, 刘林清, 刘胜春. 基于ULK1活化探讨白花蛇舌草醇诱导宫颈癌细胞线粒体损伤的机制[J]. 河北医学, 2025, 31(1): 8-14.
DUAN Jiaqi, LIU Linqing, LIU Shengchun. Mechanism of Mitochondrial Injury Induced by Alba Glossamol in Cervical Cancer Cells Based on ULK1 Activation. HeBei Med, 2025, 31(1): 8-14.
[1] Li C,Cui Z,Deng S,et al.The potential of plant extracts in cell therapy[J].Stem Cell Research & Therapy,2022,13(1):472. [2] Jabeen A,Mansoor Q,Zainab T,et al.Natural plant extracts mediated expression regulation of TGF-β receptors and SMAD genes in human cancer cell lines[J].Molecular Biology Reports,2022,49(6):4171-4178. [3] Vidhya R,Bhuminathan S,Rekha M,et al.Ravishankar.Therapeutic and pharmacological efficacy of plant Boerhaavia diffusa-a review[J].Int Appl Pharm,2022,(14):58-62. [4] Wu H,Zhang L,Wang C,et al.Network pharmacology analysis and experimental verification on antiangiogenesis mechanism of hedyotis diffusa willd in liver cancer[J].Evidence‐Based Complementary and Alternative Medicine,2023,2023(1):1416841. [5] Jiang J,Wang J,Li C,et al.Hyperoxia induces alveolar epithelial cell apoptosis by regulating mitochondrial function through small mothers against decapentaplegic 3 (SMAD3) and extracellular signal-regulated kinase 1/2 (ERK1/2)[J].Bioengineered,2022,13(1):242-252. [6] Zhang L,Qi J,Zhang X,et al.The regulatory roles of mitochondrial calcium and the mitochondrial calcium uniporter in tumor cells[J].International Journal of Molecular Sciences,2022,23(12):6667. [7] Zani A P,Zani C P,Din Z U,et al.Dibenzylideneacetone induces apoptosis in cervical cancer cells through ros-mediated mitochondrial damage[J].Antioxidants,2023,12(2):317. [8] Yang Y,Zhu Y,Zhou S,et al.TRIM27 cooperates with STK38L to inhibit ULK1‐mediated autophagy and promote tumorigenesis[J].The EMBO Journal,2022,41(14):e109777. [9] Huang Y,Liang B,Li Z,et al.Polystyrene nanoplastic exposure induces excessive mitophagy by activating AMPK/ULK1 pathway in differentiated SH-SY5Y cells and dopaminergic neurons in vivo[J].Particle and Fibre Toxicology,2023,20(1):44.
2025, Vol. 31 
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