Janarthanam Vishnu Adith, Sugumar Moogambigai, Gupta Rupesh, Alhegaili Alaa S, Guru Ajay, Issac Praveen Kumar
Institute of Biotechnology, Department of Medical Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, Tamil Nadu, India.
Chitkara University Institute of Engineering and Technology, Chitkara University, Punjab, India.
Cell Biochem Biophys. 2025 Jun 23. doi: 10.1007/s12013-025-01798-z.
Oxidative stress, caused by an imbalance between harmful prooxidants and the body's natural antioxidant defenses, plays a major role in the development of cancer. Plant-based compounds, especially polyphenols, are being widely explored for their ability to fight oxidative damage and support cancer therapy. Hamamelitannin (HAM), a natural gallotannin found in Hamamelis virginiana, has shown promising biological activity, but its effects on oxidative stress and cancer are not yet well understood. In this study, we explored the antioxidant and anticancer potential of HAM using a combination of laboratory experiments and computer-based analyses. HAM was found to scavenge free radicals effectively in several in vitro assays, including DPPH, ABTS, hydrogen peroxide, and superoxide tests. In liver cancer (HepG2) cells, HAM reduced cell viability and increased LDH release, suggesting its ability to induce cell damage selectively. It also boosted the activity of key antioxidant enzymes (SOD, CAT, GPx) and reduced oxidative stress. Gene expression analysis revealed that HAM promoted cancer cell death by increasing pro-apoptotic markers (Bax, caspase-3, caspase-9). Molecular docking showed strong interactions between HAM and several key proteins involved in oxidative stress and apoptosis, which were further supported by molecular dynamics simulations confirming stable binding. Together, these findings suggest that HAM can protect cells from oxidative damage while promoting cancer cell death, pointing to its potential as a therapeutic agent for oxidative stress-related diseases like liver cancer. Further in vivo studies are needed to fully understand its effectiveness and underlying mechanisms.
氧化应激是由有害的促氧化剂与人体天然抗氧化防御系统之间的失衡引起的，在癌症发展中起主要作用。基于植物的化合物，尤其是多酚，因其对抗氧化损伤和支持癌症治疗的能力而受到广泛研究。北美金缕梅中发现的天然没食子单宁金缕梅鞣质（HAM）已显示出有前景的生物活性，但其对氧化应激和癌症的影响尚未完全了解。在本研究中，我们结合实验室实验和基于计算机的分析，探索了HAM的抗氧化和抗癌潜力。在包括DPPH、ABTS、过氧化氢和超氧化物测试在内的多项体外实验中，发现HAM能有效清除自由基。在肝癌（HepG2）细胞中，HAM降低了细胞活力并增加了乳酸脱氢酶释放，表明其具有选择性诱导细胞损伤的能力。它还增强了关键抗氧化酶（超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶）的活性并降低了氧化应激。基因表达分析显示，HAM通过增加促凋亡标志物（Bax、半胱天冬酶-3、半胱天冬酶-9）促进癌细胞死亡。分子对接显示HAM与几种参与氧化应激和细胞凋亡的关键蛋白之间有强烈相互作用，分子动力学模拟进一步证实了稳定结合，支持了这一结果。这些研究结果共同表明，HAM可以保护细胞免受氧化损伤，同时促进癌细胞死亡，这表明它有潜力作为肝癌等氧化应激相关疾病的治疗剂。需要进一步的体内研究来充分了解其有效性和潜在机制。
