Venkatesan Kamalesh Balakumar, Srinivasan Manoj Kumar, Prasad Monisha, Jayaseelan Nivedha, Alamelu Saravanan, Panneerselvam Chellasamy, Al-Duais Mohammed A, Alasmari Abdulrahman, Ajmal Mohammad Rehan, Al-Aoh Hatem A
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamilnadu, India.
Molecular Nutrition and Genomics Lab, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai, India.
Med Oncol. 2025 Jun 27;42(8):290. doi: 10.1007/s12032-025-02835-w.
Gliomas represent one of the most aggressive and treatment-resistant brain tumors, necessitating novel therapeutic strategies. Pyrogallol, a naturally occurring polyphenol, has been reported to exhibit anticancer properties, but its effects on glioma cells remain underexplored. This study investigates the cytotoxic, apoptotic and oxidative stress-inducing effects of pyrogallol on C6 glioma cells. Using MTT assays, pyrogallol demonstrated a significant dose and time dependent cytotoxicity in C6 cells, with IC50 values decreasing from 40 µM at 24 h to 15 µM at 72 h. Morphological analyses through AO/EtBr and DAPI staining confirmed apoptosis induction, showing nuclear fragmentation and membrane blebbing in treated cells. Pyrogallol also increased intracellular reactive oxygen species (ROS) and disrupted mitochondrial membrane potential (MMP), indicating oxidative stress and mitochondrial dysfunction. Flow cytometry with Annexin V-FITC/PI staining revealed a dose-dependent increase in early and late apoptotic populations, accompanied by a significant G0/G1 phase cell cycle arrest. Biochemical assays showed elevated lipid peroxidation and reduced antioxidant enzyme activities (SOD and catalase), further supporting oxidative stress involvement. At the molecular level, qRT-PCR and ELISA analyses demonstrated upregulation of pro-apoptotic genes and proteins Bax and cytochrome c, with downregulation of the antiapoptotic marker Bcl-2, confirming pyrogallol role in promoting apoptotic pathways. These findings highlight pyrogallol's potent anticancer effects on C6 glioma cells via apoptosis induction, oxidative stress, and cell cycle arrest, suggesting its potential as a therapeutic candidate against glioma.
神经胶质瘤是最具侵袭性且最难治疗的脑肿瘤之一，因此需要新的治疗策略。连苯三酚是一种天然存在的多酚，据报道具有抗癌特性，但其对神经胶质瘤细胞的影响仍未得到充分研究。本研究调查了连苯三酚对C6神经胶质瘤细胞的细胞毒性、凋亡诱导和氧化应激诱导作用。通过MTT试验，连苯三酚在C6细胞中表现出显著的剂量和时间依赖性细胞毒性，IC50值从24小时时的40µM降至72小时时的15µM。通过AO/EtBr和DAPI染色进行的形态学分析证实了凋亡诱导，显示处理后的细胞出现核碎裂和细胞膜泡化。连苯三酚还增加了细胞内活性氧（ROS）并破坏了线粒体膜电位（MMP），表明存在氧化应激和线粒体功能障碍。用Annexin V-FITC/PI染色进行的流式细胞术显示早期和晚期凋亡细胞群体呈剂量依赖性增加，同时伴有显著的G0/G1期细胞周期阻滞。生化分析显示脂质过氧化升高，抗氧化酶活性（超氧化物歧化酶和过氧化氢酶）降低，进一步支持了氧化应激的参与。在分子水平上，qRT-PCR和ELISA分析表明促凋亡基因和蛋白Bax及细胞色素c上调，抗凋亡标志物Bcl-2下调，证实了连苯三酚在促进凋亡途径中的作用。这些发现突出了连苯三酚通过诱导凋亡、氧化应激和细胞周期阻滞对C6神经胶质瘤细胞产生的强大抗癌作用，表明其作为神经胶质瘤治疗候选药物的潜力。
