Hernandez-Valencia Carmen G, Rodriguez-Martinez Griselda, Carriles-Perez Andres M, Gonzalez-Perez Daniel, Ortega-Sanchez Carmina, Andonegui-Elguera Marco A, Zamudio-Cuevas Yessica, Fernandez-Torres Javier, Hernandez-Valdepena Miguel A, Gimeno Miquel, Sanchez-Sanchez Roberto
Departamento de Alimentos y Biotecnología, Facultad de Química, UNAM, Mexico City, Mexico.
Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City, Mexico.
Anticancer Res. 2024 Mar;44(3):1201-1208. doi: 10.21873/anticanres.16915.
BACKGROUND/AIM: Enzyme-mediated grafting of poly (gallic acid) (PGAL) and L-arginine and a-L-lysine onto PGAL produces reactive oxygen species (ROS)-suppressor multiradical molecules with low cytotoxicity, high thermostability and water solubility with cancer treatment potential. This study examined the anticancer effects of these molecules in hepatic (HepG2, ATCC HB-8065), breast (MCF7, ATCC HTB-22), and prostate (PC-3, ATCC CRL-1435 and DU 145, ATCC HTB-81) cancer cell lines, as well as in fibroblasts from healthy human skin as control cells.
PGAL was synthesized by the oxidative polymerization of the naturally abundant GA using laccase from Trametes versicolor. Insertions of amino acids L-arginine and α-L-lysine on the PGAL chain were carried out by microwave. The cells of dermal fibroblast (Fb) were obtained from primary skin cultures and isolated from skin biopsies. The cancer cells lines of hepatic (HepG2), breast (MCF7), and prostate (PC-3, DU 145) were obtained from ATCC. The viability of the cancer cells and the primary culture was obtained by the MTT assay. Proliferation was demonstrated by crystal violet assay. Cell migration was determined by Wound healing assay. Finally, cell cycle analysis was carried out with cells.
The results show that 200 μg/ml of PGAL cultured in vitro with prostate cancer cells decreased viability, proliferation, and migration, as well as arrested cells in the G and S phases of the cell cycle. In contrast, the dermal fibroblasts and the hepatic line remained unaffected. The random grafting of L-Arg and a-L-Lys onto the PGAL chain also decreased the viability of prostate cancer cells.
PGAL and PGAL-grafted amino acids are potential adjuvants for prostate cancer treatment, with improved physicochemical characteristics compared to GA.
背景/目的:通过酶介导将聚(没食子酸)(PGAL)与L-精氨酸和α-L-赖氨酸进行接枝,可产生具有低细胞毒性、高热稳定性和水溶性且具有癌症治疗潜力的活性氧(ROS)抑制多自由基分子。本研究检测了这些分子对肝癌(HepG2,ATCC HB-8065)、乳腺癌(MCF7,ATCC HTB-22)和前列腺癌(PC-3,ATCC CRL-1435和DU 145,ATCC HTB-81)细胞系以及健康人皮肤成纤维细胞(作为对照细胞)的抗癌作用。
利用云芝漆酶通过天然丰富的没食子酸(GA)的氧化聚合反应合成PGAL。通过微波将氨基酸L-精氨酸和α-L-赖氨酸插入PGAL链上。真皮成纤维细胞(Fb)细胞取自原代皮肤培养物,并从皮肤活检组织中分离得到。肝癌(HepG2)、乳腺癌(MCF7)和前列腺癌(PC-3、DU 145)细胞系购自美国典型培养物保藏中心(ATCC)。通过MTT法检测癌细胞和原代培养物的活力。通过结晶紫法证明细胞增殖情况。通过伤口愈合试验测定细胞迁移能力。最后,对细胞进行细胞周期分析。
结果表明,在体外与前列腺癌细胞一起培养的200μg/ml PGAL可降低细胞活力、增殖能力和迁移能力,并使细胞停滞在细胞周期的G期和S期。相比之下,真皮成纤维细胞和肝癌细胞系未受影响。L-精氨酸和α-L-赖氨酸随机接枝到PGAL链上也降低了前列腺癌细胞的活力。
PGAL和接枝氨基酸的PGAL是前列腺癌治疗的潜在佐剂,与GA相比具有改善的理化特性。