Department of Biotechnology, Era's Lucknow Medical College & Hospital, Era University, Lucknow, India.
Department of Biochemistry, King George's Medical University, Lucknow, India.
J Food Biochem. 2021 May;45(5):e13720. doi: 10.1111/jfbc.13720. Epub 2021 Apr 15.
Moringa oleifera is an excellent source of phenolics and flavonoids comprise various pharmacological activities. The fourth widespread leading cause of the patients' death is liver cancer. This study was formulated to perform the antiproliferative activity of Moringa oleifera fruit (MOF) extract on human liver cancer HepG2 cells and computational validation of cell death. HepG2 cell line was treated with 25, 50, 75, 100, and 200 µg/ml of MOF extract for 48 hr, and antiproliferative activity was analyzed using MTT assay, nuclear condensation, annexin V-FITC/PI double stain, ROS generation, and apoptosis executioner enzyme caspase-3. MOF extract reduced the cell viability significantly (p ˂ .05) by increasing cellular apoptosis which was confirmed by annexin V-FITC/PI staining assay. In addition, MOF stimulated intracellular ROS production and subsequently induced caspase-3 activity depending upon dose. In silico analysis revealed the good binding interaction between amino acid residues of caspase-3 (PDB ID: 1GFW) protein and selected active constituents of MOF. PASS analyses of the phytoconstituents showed no violation of Lipinski's rule of five. Analysis of drug-likeness and toxicity measurement exhibited drug-like candidates with no predicted toxicity. In conclusion, this study showed the potential anticancer activity of MOF extract which may be valuable source for anticancer drug development. PRACTICAL APPLICATIONS: Moringa oleifera fruit extract induced the anti-proliferative activity against human hepatocellular carcinoma HepG2 cells through ROS-mediated apoptosis and activation of caspase-3 enzyme. Structure-based virtual screening study between bioactive components of Moringa oleifera fruits and apoptosis executioner caspase-3 enzyme has validated the anti-proliferative activity of Moringa oleifera fruit extract. Interestingly, active phytoconstituents of Moringa oleifera fruit exhibited drug-like candidates with no predicted toxicity. Thus, Moringa oleifera fruit could be used as valuable source for anticancer drug development against human liver cancer with relatively non-toxic to healthy cells.
辣木是酚类和类黄酮的极好来源，具有多种药理活性。 肝癌是导致患者死亡的第四大常见原因。 本研究旨在研究辣木果实（MOF）提取物对人肝癌 HepG2 细胞的抗增殖活性，并对细胞死亡进行计算验证。 将 HepG2 细胞系用 25、50、75、100 和 200μg/ml 的 MOF 提取物处理 48 小时，并用 MTT 测定法、核浓缩、Annexin V-FITC/PI 双重染色、ROS 生成和凋亡执行酶 caspase-3 分析抗增殖活性。 MOF 提取物通过增加细胞凋亡显着降低细胞活力（p<.05），这通过 Annexin V-FITC/PI 染色测定法得到证实。 此外，MOF 刺激细胞内 ROS 生成，并随后根据剂量诱导 caspase-3 活性。 计算机分析显示 caspase-3（PDB ID：1GFW）蛋白的氨基酸残基与 MOF 中选定的活性成分之间具有良好的结合相互作用。 植物成分的 PASS 分析显示没有违反 Lipinski 的五规则。 药物相似性和毒性测量分析显示出无预测毒性的药物样候选物。 总之，本研究表明 MOF 提取物具有潜在的抗癌活性，可能是抗癌药物开发的有价值来源。 实际应用：辣木果实提取物通过 ROS 介导的细胞凋亡和 caspase-3 酶的激活诱导对人肝癌 HepG2 细胞的抗增殖活性。 辣木果实生物活性成分与凋亡执行酶 caspase-3 之间的基于结构的虚拟筛选研究验证了辣木果实提取物的抗增殖活性。 有趣的是，辣木果实的活性植物成分表现出无预测毒性的药物样候选物。 因此，辣木果实可以作为抗癌药物开发的有价值来源，用于治疗人类肝癌，对健康细胞的毒性相对较低。
