Department of Biophysics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
J Pineal Res. 2012 Aug;53(1):91-8. doi: 10.1111/j.1600-079X.2012.00974.x. Epub 2012 Jan 31.
Melatonin has antitumor activity via several mechanisms including its antiproliferative and proapoptotic effects in addition to its potent antioxidant action. Thus, melatonin has proven useful in the treatment of tumors in association with chemotherapeutic drugs. This study was performed to evaluate the effect of melatonin on the cytotoxicity and apoptosis induced by three different chemotherapeutic agents, namely 5-fluorouracil (5-FU), cisplatin, and doxorubicin in the rat pancreatic tumor cell line AR42J. We found that both melatonin and the three chemotherapeutic drugs induce a time-dependent decrease in AR42J cell viability, reaching the highest cytotoxic effect after 48 hr of incubation. Furthermore, melatonin significantly augmented the cytotoxicity of the chemotherapeutic agents. Consistently, cotreatment of AR42J cells with each of the chemotherapeutic agents in the presence of melatonin increased the population of apoptotic cells, elevated mitochondrial membrane depolarization, and augmented intracellular reactive oxygen species (ROS) production compared to treatment with each chemotherapeutic agent alone. These results provide evidence that in vitro melatonin enhances chemotherapy-induced cytotoxicity and apoptosis in rat pancreatic tumor AR42J cells and, therefore, melatonin may be potentially applied to pancreatic tumor treatment as a powerful synergistic agent in combination with chemotherapeutic drugs.
褪黑素通过多种机制具有抗肿瘤活性，除了其强大的抗氧化作用外，还具有抗增殖和促凋亡作用。因此，褪黑素已被证明在与化疗药物联合治疗肿瘤方面非常有用。本研究旨在评估褪黑素对三种不同化疗药物，即 5-氟尿嘧啶（5-FU）、顺铂和阿霉素在大鼠胰腺肿瘤细胞系 AR42J 中诱导的细胞毒性和细胞凋亡的影响。我们发现，褪黑素和三种化疗药物均诱导 AR42J 细胞活力随时间呈依赖性下降，孵育 48 小时后达到最高细胞毒性效应。此外，褪黑素显著增强了化疗药物的细胞毒性。一致地，与每种化疗药物单独处理相比，在用每种化疗药物处理的同时用褪黑素处理 AR42J 细胞增加了凋亡细胞的群体、提高了线粒体膜去极化，并增加了细胞内活性氧（ROS）的产生。这些结果提供了证据表明，褪黑素在体外增强了大鼠胰腺肿瘤 AR42J 细胞中化疗诱导的细胞毒性和细胞凋亡，因此，褪黑素可能作为一种与化疗药物联合使用的强大协同剂潜在应用于胰腺肿瘤治疗。
