Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Molecules. 2023 Nov 30;28(23):7871. doi: 10.3390/molecules28237871.
Globally, prostate cancer is among the most threatening and leading causes of death in men. This study, therefore, aimed to search for an ideal antitumor strategy with high efficacy, low drug resistance, and no or few adverse effects. Resistomycin is a natural antibiotic derived from marine actinomycetes, and it possesses various biological activities. Prostate cancer cells (PC3) were treated with resistomycin (IC.: 0.65 or IC: 1.3 µg/mL) or 5-fluorouracil (5-FU; IC: 7 µg/mL) for 24 h. MTT assay and flow cytometry were utilized to assess cell viability and apoptosis. Oxidative stress, apoptotic-related markers, and cell cycle were also assessed. The results revealed that the IC of resistomycin and 5-FU on PC3 cells were 2.63 µg/mL and 14.44 µg/mL, respectively. Furthermore, treated cells with the high dose of resistomycin showed an increased number of apoptotic cells compared to those treated with the lower dose. Remarkable induction of reactive oxygen species generation and lactate dehydrogenase (LDH) leakage with high malondialdehyde (MDA), carbonyl protein (CP), and 8-hydroxyguanosine (8-OHdG) contents were observed in resistomycin-treated cells. In addition, marked declines in glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in PC3 cells subjected to resistomycin therapy were observed. Resistomycin triggered observable cell apoptosis by increasing Bax, caspase-3, and cytosolic cytochrome c levels and decreasing Bcl-2 levels. In addition, notable downregulation of proliferating cell nuclear antigen (PCNA) and cyclin D1 was observed in resistomycin-treated cancerous cells. According to this evaluation, the antitumor potential of resistomycin, in a concentration-dependent manner, in prostate cancer cells was achieved by triggering oxidative stress, mitochondrial apoptosis, and cell cycle arrest in cancer cells. In conclusion, our investigation suggests that resistomycin can be considered a starting point for developing new chemotherapeutic agents for human prostate cancer.
在全球范围内，前列腺癌是男性最具威胁性和主要的死亡原因之一。因此，本研究旨在寻找一种疗效高、耐药性低、不良反应少或无的理想抗肿瘤策略。 resistomycin 是一种从海洋放线菌中提取的天然抗生素，具有多种生物活性。将前列腺癌细胞（PC3）用 resistomycin（IC：0.65 或 IC：1.3 µg/mL）或 5-氟尿嘧啶（5-FU；IC：7 µg/mL）处理 24 小时。采用 MTT 法和流式细胞术检测细胞活力和细胞凋亡。还评估了氧化应激、凋亡相关标志物和细胞周期。结果表明，resistomycin 和 5-FU 对 PC3 细胞的 IC 分别为 2.63 µg/mL 和 14.44 µg/mL。此外，与低剂量处理的细胞相比，高剂量 resistomycin 处理的细胞中凋亡细胞数量增加。与低剂量处理的细胞相比，用高剂量 resistomycin 处理的细胞中观察到活性氧（ROS）生成和乳酸脱氢酶（LDH）漏出量显著增加，同时还观察到丙二醛（MDA）、羰基蛋白（CP）和 8-羟基鸟苷（8-OHdG）含量显著增加。此外，在用 resistomycin 治疗的 PC3 细胞中观察到谷胱甘肽（GSH）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）水平明显下降。Resistomycin 通过增加 Bax、caspase-3 和细胞质细胞色素 c 水平以及降低 Bcl-2 水平，诱导细胞凋亡。此外，在 resistomycin 处理的癌细胞中，增殖细胞核抗原（PCNA）和细胞周期蛋白 D1 的表达明显下调。综上所述，resistomycin 以浓度依赖的方式在前列腺癌细胞中发挥抗肿瘤作用，通过触发氧化应激、线粒体凋亡和细胞周期阻滞来杀死癌细胞。总之，我们的研究表明，resistomycin 可以作为开发人类前列腺癌新化疗药物的起点。
Zotero 插件
