Vijayakumar Sekar, González-Sánchez Zaira I, Anbu Periasamy, Divya Mani, Sonamuthu Jegatheeswaran, Rajkumar Mangaiyarkarasi, Durán-Lara Esteban F, Peng Yonggang, Yu Ying, Li Mingchun
College of Material Science and Engineering, Huaqiao University, Engineering Research Center of Environment-Friendly Functional Materials, Ministry of Education, Xiamen, 361021, PR China.
Nanobiology Laboratory, Department of Natural and ExactSciences, Pontificia Universidad Católica Madre y Maestra, PUCMM, Autopista Duarte Km 1 ½, Santiago de los Caballeros, Dominican Republic; Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, Seville, Spain.
Int J Biol Macromol. 2025 Sep 10;328(Pt 2):147597. doi: 10.1016/j.ijbiomac.2025.147597.
In recent years, gastric cancer was the fifth most prevalent cancer worldwide and responsible for thousands of deaths worldwide. Despite advances in early detection and treatment, high mortality rates persist due to resistance to conventional chemotherapy and disease recurrence. Green-synthesized zinc oxide nanoparticles (ZnO NPs) have arisen as promising candidates for anticancer therapy because of their biocompatibility and targeted cytotoxicity. This study presents a cost-effective, green synthesis of ZnO NPs using asafoetida gum as a stabilizing agent. The chemical composition of asafoetida gum was analyzed using gas chromatography/mass spectrometry (GC/MS).GC/MS analysis found the principal constituents of asafoetida gum as follows: cis-4-Decenal (92.8 %), 2-Methoxy-4-vinylphenol (91.6 %), 2-Decenal (E) (89.5 %), 10,12-Octadecadiynoic acid (84.6 %), 8-epi-gamma-eudesmol (81.3 %), and Eudesma-5,11(13)-dien-8,12-olide (80.2 %).The resulting AS-ZnO NPs, with a quasi-spherical morphology and an average size of 98.42 nm, appeared as a milky-white powder. Cytotoxicity analysis (MTT assay) demonstrated that AS-ZnO NPs significantly decreased the viability of human gastric cancer (AGS) cells at 100 μg/mL, while exhibiting no cytotoxicity in normal mouse embryonic fibroblast (NIH3T3) cells. The anticancer activity was linked to increased production of reactive oxygen species (ROS), which produces mitochondrial dysfunction and nuclear damage, as confirmed by ROS assays, mitochondrial membrane potential analysis, and DAPI staining. Apoptotic evaluation by acridine orange/ethidium bromide (AO/EtBr) staining and flow cytometry further corroborated that AS-ZnO NPs induced apoptosis in AGS cells. The double staining of Annexin V / FITC revealed both apoptotic and necrotic cell death, validating the activation of apoptosis as the primary mechanism of cytotoxicity. These results indicate that AS-ZnO NPs hold promise as potential therapeutic agents for gastric cancer treatment. The ecofriendly synthesis approach avoids toxic chemicals, making it scalable and suitable for biomedical applications. However, more in silico, preclinical and clinical research is necessary to assess their efficacy and safety for medical applications.
近年来,胃癌是全球第五大常见癌症,在全球导致数千人死亡。尽管早期检测和治疗取得了进展,但由于对传统化疗的耐药性和疾病复发,高死亡率仍然存在。绿色合成的氧化锌纳米颗粒(ZnO NPs)因其生物相容性和靶向细胞毒性,已成为抗癌治疗的有希望的候选者。本研究提出了一种使用阿魏胶作为稳定剂的经济高效的ZnO NPs绿色合成方法。使用气相色谱/质谱联用仪(GC/MS)分析了阿魏胶的化学成分。GC/MS分析发现阿魏胶的主要成分如下:顺式-4-癸烯醛(92.8%)、2-甲氧基-4-乙烯基苯酚(91.6%)、(E)-2-癸烯醛(89.5%)、10,12-十八碳二炔酸(84.6%)、8-表-γ-桉叶醇(81.3%)和桉叶-5,11(13)-二烯-8,12-内酯(80.2%)。所得的AS-ZnO NPs呈准球形形态,平均尺寸为98.42 nm,呈乳白色粉末状。细胞毒性分析(MTT试验)表明,AS-ZnO NPs在100μg/mL时显著降低了人胃癌(AGS)细胞的活力,而在正常小鼠胚胎成纤维细胞(NIH3T3)中未表现出细胞毒性。抗癌活性与活性氧(ROS)生成增加有关,ROS会导致线粒体功能障碍和核损伤,这已通过ROS检测、线粒体膜电位分析和DAPI染色得到证实。通过吖啶橙/溴化乙锭(AO/EtBr)染色和流式细胞术进行的凋亡评估进一步证实,AS-ZnO NPs可诱导AGS细胞凋亡。膜联蛋白V/FITC双染显示了凋亡和坏死性细胞死亡,验证了凋亡激活是细胞毒性的主要机制。这些结果表明,AS-ZnO NPs有望成为治疗胃癌的潜在治疗剂。这种环保的合成方法避免了使用有毒化学物质,使其具有可扩展性,适用于生物医学应用。然而,需要更多的计算机模拟、临床前和临床研究来评估它们在医学应用中的疗效和安全性。