Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Nanomedicine & Nanobiotechnology Lab, Department of Biosciences, Integral University, Lucknow 226026, India.
Bioorg Chem. 2021 Feb;107:104626. doi: 10.1016/j.bioorg.2021.104626. Epub 2021 Jan 7.
Vincamine, a well-known plant alkaloid, has been used as a dietary supplement and as a peripheral vasodilator to combat aging in humans. In this study, for the very first time, we demonstrated that vincamine can function as an anticancer agent in a human alveolar basal epithelial cell line A549 (IC = 309.7 μM). The anticancer potential of vincamine in A549 cells was assessed by molecular assays to determine cell viability, generation of intracellular ROS, nuclear condensation, caspase-3 activity and inhibition, and change in mitochondrial membrane potential (ΔΨm). In silico studies predicted that the anti-proliferative potential of vincamine is enhanced by its interaction with the apoptotic protein caspase-3, and that this interaction is driven by two hydrogen bonds and has a high free energy of binding (-5.64 kcal/mol) with an estimated association constant (K) of 73.67 μM. We found that vincamine stimulated caspase-3-dependent apoptosis and lowered mitochondrial membrane potential, which ultimately led to cytochrome C release. Vincamine was also found to quench hydroxyl free radicals and deplete iron ions in cancer cells. As a dietary supplement, vincamine is almost non-toxic in BEAS-2B and 3T3-L1 cells. Therefore, we propose that vincamine represents a safe anticancer agent in lung cancer cells. Its role in other cancers has yet to be explored.
长春胺，一种著名的植物生物碱，已被用作膳食补充剂和外周血管扩张剂，以抵抗人类衰老。在这项研究中，我们首次证明长春胺可以作为一种抗癌剂在人类肺泡基底上皮细胞系 A549（IC=309.7 μM）中发挥作用。长春胺在 A549 细胞中的抗癌潜力通过分子测定来评估，以确定细胞活力、细胞内 ROS 的产生、核浓缩、半胱天冬酶-3 活性和抑制以及线粒体膜电位（ΔΨm）的变化。计算研究预测，长春胺与凋亡蛋白半胱天冬酶-3 的相互作用增强了其增殖潜力，这种相互作用由两个氢键驱动，具有-5.64 kcal/mol 的高结合自由能，估计结合常数（K）为 73.67 μM。我们发现长春胺刺激半胱天冬酶-3 依赖性细胞凋亡并降低线粒体膜电位，最终导致细胞色素 C 释放。长春胺还被发现能猝灭羟自由基并耗尽癌细胞中的铁离子。作为膳食补充剂，长春胺在 BEAS-2B 和 3T3-L1 细胞中几乎无毒。因此，我们提出长春胺在肺癌细胞中是一种安全的抗癌剂。它在其他癌症中的作用尚未被探索。
