Department of Biotechnology, Era's Lucknow Medical College & Hospital, Era University, Lucknow 226003, India.
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, Saudi Arabia.
Anticancer Agents Med Chem. 2021;21(18):2536-2545. doi: 10.2174/1871520621666210210103729.
Cervical cancer is the second leading cause of cancer in women, which necessitates safe and potential therapeutic agents.
This study was designed to investigate the antiproliferative effect of ethanolic extract of Cissus quadrangularis L. (CQ) against human cervical adenocarcinoma HeLa cell line and in silico analysis of selected active agents against apoptosis executioner enzyme caspase-3.
Cell viability was analyzed in HeLa cells at different concentrations (25-300 μg/ml) of CQ extract. Reactive oxygen species (ROS) generation, cellular apoptosis, cell cycle analysis and caspases-3 activation were evaluated. In silico, structure-based virtual screening analysis was carried out using AutoDock Vina and iGEMDOCK.
Cell viability of HeLa cells was reduced significantly (p < 0.05) in a dose-dependent manner, however, CQ extract showed non-toxic to normal kidney epithelial NRK-52E cells. CQ extract induced the intracellular ROS level, nuclear condensation and reduced the mitochondrial membrane potential (MMP) with the induction of annexin V-FITC positive cells. CQ extract arrested cells in G0/G1 and G2/M checkpoints and activated caspase-3 activity significantly in HeLa cells. The molecular docking study showed a strong binding affinity of CQ phytocomponents against the caspase-3 (PDB ID: 1GFW) protein of human apoptosis. PASS analyses of selected active components using Lipinski's Rule of five showed promising results. Further, drug-likeness and toxicity assessment using OSIRIS Data Warrior V5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity.
This study suggested that active constituents in CQ extract can be considered as potential chemotherapeutic candidates in the management of cervical cancer.
宫颈癌是女性癌症中的第二大常见疾病，因此需要安全且有潜力的治疗药物。
本研究旨在探讨筋骨草（CQ）乙醇提取物对人宫颈腺癌 HeLa 细胞系的增殖抑制作用，并对选定的凋亡执行酶 caspase-3 的活性成分进行计算机模拟分析。
在不同浓度（25-300μg/ml）的 CQ 提取物作用下，用细胞活力分析法检测 HeLa 细胞活力。评估活性氧（ROS）生成、细胞凋亡、细胞周期分析和 caspase-3 激活。在计算机模拟中，使用 AutoDock Vina 和 iGEMDOCK 进行基于结构的虚拟筛选分析。
HeLa 细胞的细胞活力呈浓度依赖性显著降低（p<0.05），然而，CQ 提取物对正常肾上皮 NRK-52E 细胞无毒性。CQ 提取物诱导细胞内 ROS 水平升高、核浓缩和降低线粒体膜电位（MMP），同时诱导 Annexin V-FITC 阳性细胞。CQ 提取物使 HeLa 细胞停滞在 G0/G1 和 G2/M 检查点，并显著激活 caspase-3 活性。分子对接研究表明，CQ 植物成分对人凋亡的 caspase-3（PDB ID：1GFW）蛋白具有很强的结合亲和力。使用 Lipinski 的五规则对选定的活性成分进行 PASS 分析显示出有希望的结果。进一步，使用 OSIRIS Data Warrior V5.2.1 软件进行药物相似性和毒性评估，显示植物成分作为候选药物具有可行性，且无预测毒性。
本研究表明，CQ 提取物中的活性成分可作为宫颈癌治疗的潜在化疗候选药物。
