当前位置: X-MOL 学术BMC Mol. Cell Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Effect of Voacamine upon inhibition of hypoxia induced fatty acid synthesis in a rat model of methyln-nitrosourea induced mammary gland carcinoma
BMC Molecular and Cell Biology ( IF 2.8 ) Pub Date : 2021-06-05 , DOI: 10.1186/s12860-021-00371-9
Lakhveer Singh 1 , Manjari Singh 2 , Shubham Rastogi 1 , Anurag Choudhary 1 , Dinesh Kumar 3 , Ritu Raj 3 , Mohd Nazam Ansari 4 , Abdulaziz S Saeedan 4 , Gaurav Kaithwas 1
Affiliation  

In the present study, fatty acid synthesis is targeted to combat mammary gland carcinoma by activating prolyl hydroxylase-2 with Voacamine alone and in combination with Tamoxifen. It was hypothesized that the activation of prolyl hydroxylase-2 would inhibit the hypoxia-induced fatty acid synthesis and mammary gland carcinoma. Mammary gland carcinoma was induced with a single dose administration of N-methyl-N-nitrosourea (50 mg/kg,i.p.) and treatment with Voacamine and Tamoxifen 15 days after carcinogen administration. At the end of the study, hemodynamic profiling of animals was recorded to assess the cardiotoxic potential of the drug. Blood serum was separated and subjected to nuclear magnetic resonance spectroscopy. Carmine staining and histopathology of mammary gland tissue were performed to evaluate the anti-angiogenic potential of the drug. The antioxidant potential of the drug was measured with antioxidant markers. Western blotting was performed to study the effect of the drug at the molecular level. Results of the study have shown that Voacamine treatment stopped further decrease in body weight of experimental animals. The hemodynamic study evidenced that Voacamine at a low dose is safe in cardiac patients. Microscopic evaluation of mammary gland tissue documented the anti-angiogenic potential of Voacamine and Tamoxifen therapy. Perturbed serum metabolites were also restored to normal along with antioxidant markers. Immunoblotting of mammary gland tissue also depicted restoration of proteins of the hypoxic and fatty acid pathway. Conclusively, Voacamine and its combination with Tamoxifen activated prolyl hydroxylase-2 to combat mammary gland carcinoma.

中文翻译:

伏安卡明对甲基亚硝基脲诱发乳腺癌大鼠模型缺氧诱导脂肪酸合成的抑制作用

在本研究中,脂肪酸合成的目标是通过单独使用 Voacamine 和与他莫昔芬联合激活脯氨酰羟化酶-2 来对抗乳腺癌。假设脯氨酰羟化酶-2 的激活会抑制缺氧诱导的脂肪酸合成和乳腺癌。在致癌物给药后 15 天,通过单剂量给药 N-甲基-N-亚硝基脲 (50 mg/kg, ip) 并用 Voacamine 和他莫昔芬治疗诱发乳腺癌。在研究结束时,记录动物的血流动力学分析以评估药物的心脏毒性潜力。分离血清并进行核磁共振波谱分析。对乳腺组织进行胭脂红染色和组织病理学检查以评估药物的抗血管生成潜力。药物的抗氧化潜力是用抗氧化标志物测量的。进行蛋白质印迹以在分子水平上研究药物的作用。研究结果表明,Voacamine 治疗阻止了实验动物体重的进一步下降。血液动力学研究证明,低剂量的 Voacamine 对心脏病患者是安全的。乳腺组织的显微镜评估记录了 Voacamine 和他莫昔芬治疗的抗血管生成潜力。扰动的血清代谢物也与抗氧化标记物一起恢复正常。乳腺组织的免疫印迹也描述了缺氧和脂肪酸途径蛋白质的恢复。最后,Voacamine 及其与他莫昔芬的组合激活脯氨酰羟化酶-2 以对抗乳腺癌。
更新日期:2021-06-05
down
wechat
bug