Cui Peilin, Luo Zhaohua, Zhang Honggang, Su Yan, Li Ailing, Li Hongwei, Zhang Jing, Yang Zhaoxu, Xiu Ruijuan
Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing.
J Pineal Res. 2006 Nov;41(4):358-62. doi: 10.1111/j.1600-079X.2006.00375.x.
Melatonin is the major secretory product of the pineal gland and is considered an important natural oncostatic agent. The anticancer activity of melatonin is due to its immunomodulatory, anti-proliferative and antioxidative effects. At present there are no direct data available as to melatonin's possible influence on angiogenesis, which is a major biological mechanism responsible for tumor growth and dissemination. The current study investigated the influence of melatonin on angiogenesis. Human umbilical vein endothelial cells (HUVECs) were cultured, identified, and purified. Cell growth and viability, DNA fragmentation and cell cycle analyses were determined. To elucidate the mechanism of action of melatonin, Western blot analyses for P53, Bax and Bcl-2 expression were carried out. The results demonstrate the anti-proliferative and apoptosis-inducing effects of melatonin; these changes were associated with cell cycle arrest, upregulation of P53 and Bax and downregulation of Bcl-2. Taken together, our data showed that melatonin in high concentrations markedly reduces HUVECs proliferation, induces cellular apoptosis, and modulates cell cycle length. P53 and Bax/Bcl-2 expression changes may be involved in these actions of melatonin.
褪黑素是松果体的主要分泌产物,被认为是一种重要的天然抑癌剂。褪黑素的抗癌活性归因于其免疫调节、抗增殖和抗氧化作用。目前尚无关于褪黑素对血管生成可能影响的直接数据,而血管生成是肿瘤生长和扩散的主要生物学机制。本研究调查了褪黑素对血管生成的影响。对人脐静脉内皮细胞(HUVECs)进行培养、鉴定和纯化。测定细胞生长和活力、DNA片段化及细胞周期分析。为阐明褪黑素的作用机制,进行了P53、Bax和Bcl-2表达的蛋白质印迹分析。结果表明褪黑素具有抗增殖和诱导凋亡的作用;这些变化与细胞周期停滞、P53和Bax上调以及Bcl-2下调有关。综上所述,我们的数据表明高浓度褪黑素可显著降低HUVECs增殖,诱导细胞凋亡,并调节细胞周期长度。P53和Bax/Bcl-2表达变化可能参与了褪黑素的这些作用。