Meher Rajesh K, Naik Manas Ranjan, Bastia Banajit, Naik Pradeep K
Department of Biotechnology & Bioinformatics, Sambalpur University, Jyoti Vihar - 768 019, Sambalpur, Odisha.
Department of Pharmacology, VSS Institute of Medical Science & Research, Burla, Sambalpur, Odisha.
Bioinformation. 2018 May 31;14(5):236-240. doi: 10.6026/97320630014236. eCollection 2018.
Angiogenesis, the formation of new capillaries from pre-existing vessels, is essential for tumor progression. Synthetic derivatives of anti-cancer compound, noscapine (an opium alkaloid) such as Cl-noscapine, Br-noscapine and Folate-noscapine along with two of the reference compounds, TNP-470 and paclitaxel were examined for anti-angiogenic activities by using human umbilical vein endothelial cells (HUVECs). The noscapine derivatives showed anti-angiogenic activity albeit at high concentration compared to the reference compounds. All the tested compounds inhibited angiogenesis in a dose-dependent manner; the drug concentration causing 50% inhibition of cell survival was 11.87 μM for Cl-noscapine, 6.9 μM for Br-noscapine and 6.79 μM for folate-noscapine. Besides, all the noscapine derivatives significantly inhibited cord formation (IC50 for Cl-noscapine is 50.76 μM, for Br-noscapine is 90.08 μM and for folate-noscapine is 18.44 μM) as well as migration and invasion (IC50 value of Cl-noscapine is 28.01 μM, for Br-noscapine is 19.78 μM and for folate-noscapine is 10.76 μM) of endothelial cells. Based on these results, we speculated that the inhibitory effects on human endothelial cell proliferation of noscapine derivatives might be important for anti-angiogenesis.
血管生成，即从已有的血管形成新的毛细血管，是肿瘤进展所必需的。使用人脐静脉内皮细胞（HUVECs），研究了抗癌化合物那可丁（一种鸦片生物碱）的合成衍生物，如氯那可丁、溴那可丁和叶酸那可丁，以及两种参考化合物TNP-470和紫杉醇的抗血管生成活性。与参考化合物相比，那可丁衍生物虽在高浓度时才显示出抗血管生成活性。所有测试化合物均以剂量依赖性方式抑制血管生成；导致细胞存活率50%抑制的药物浓度，氯那可丁为11.87μM，溴那可丁为6.9μM，叶酸那可丁为6.79μM。此外，所有那可丁衍生物均显著抑制内皮细胞的成管作用（氯那可丁的IC50为50.76μM，溴那可丁为90.08μM，叶酸那可丁为18.44μM）以及迁移和侵袭（氯那可丁的IC50值为28.01μM，溴那可丁为19.78μM，叶酸那可丁为10.76μM）。基于这些结果，我们推测那可丁衍生物对人内皮细胞增殖的抑制作用可能对抗血管生成具有重要意义。
