Anticancer Activities of Saponins and Quinones Group through Oxidative Stress and Glycolysis Inhibition via in Silico Studies
Haris Nur Mustofa1
, Hesti Lina Wiraswati1, 2*, Savira Ekawardhani1,2, Pandji Irani Fianza3and Sarasati Windria41Oncology and Stem Cell Working Group, Faculty of Medicine, Universitas Padjadjaran, 45363, Jatinangor, Jawa Barat, Indonesia
2Parasitology Division, Department of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, 45363, Jatinangor, Jawa Barat, Indonesia
3Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran, 45363, Jatinangor, Jawa Barat, Indonesia
4Infection Study Centre, Faculty of Medicine, Universitas Padjadjaran, 45363, Jatinangor, Jawa Barat, Indonesia
Corresponding Author E-mail : hesti.lina@unpad.ac.id
Abstract: One of the known causes of cancer is imbalance production between reactive oxygen species (ROS) and antioxidant defense within the cell. Under oxidative stress conditions, excessive ROS production ultimately induces cell death via apoptosis or necrosis. Moreover cancer cells use glycolysis for energy production. Glycolysis inhibition will lead to cancer cell proliferation disruption. Quinones and saponins are chemical compounds that have anticancer properties. Saponin is one of the plant’s metabolites, which also found in Indonesian medicinal plants. Preliminary studies in our lab showed that there were some species of medicinal plants in Indonesia that contained saponin, in which saponin known to have a good effect on inhibiting cancer cells. This study was aimed to know the anticancer activities from the compound that contains saponin and quinone as its active substance through the oxidative stress induction and glycolysis inhibition mechanism using in silico method. This research started by choosing the protein crystal structure of cytochrome p450 reductase (CYP450R) enzyme and pyruvate kinase M2 (PKM2) enzyme, then preparation of the protein with the help of Chimera 1.14.rc software, preparation of the ligands which belongs to cytotoxic molecule and optimization of their structure using Marvin Sketch software, and validation of molecular docking and docking process of the testing ligands on CYP450R and PKM2 enzymes using AutoDock Vina software. The results showed that testing ligands had affinity energy and good interaction with CYP450R and PKM2 enzymes, especially diosgenin. Testing ligands tended to interact with CYP450R rather than PKM2. Molecular interaction between testing ligands with the enzymes may provoke excessive ROS production and inhibit the glycolysis process in cancer cells. Compared to glycolysis inhibition, testing ligands had greater capacity in causing oxidative stress. Perhaps this study will motivate others for discovered the potential activity of medicinal plants in Indonesia.
Keywords: Anticancer; Glycolysis; Molecular Docking; Oxidative Stress; Quinone; Saponin Back to TOC