Lisdiana Lisdiana, Retno Sri Iswari, Wulan Christijanti, Harjono Harjono, Fitri Arum Sasi, Muchamad Dafip
Tomatidine is an alkaloid-steroid contained in tomato plant organs that potentially developed as an anti-cancer molecule. However, inappropriate use of solvents is frequently becoming an obstacle in the extractions process. In addition, the mechanism of action of tomatidine in the inhibition of cancer cell signaling pathways needs to be investigated. Therefore, this research aims to discover an appropriate solvent to extract tomatidine effectively, and to analyze the inhibition mechanism of tomatidine against the cancer growth pathway. A total of 80 kg of fresh tomatoes were cut into pieces and steamed at 120 °C for 30 min, then mashed and soaked for 3 days in 70 % ethanol, aquadest, petroleum ether, and chloroform separately, continued with GC/MS analysis. Molecular docking was conducted using targeted proteins including B-Raf proto-oncogen serine/ threonine protein kinase (BRAF), Vascular endothelial growth factor A (VEGFA), Smoothened protein (SMO), Cyclin-dependent kinase 2 (CDK2), and Tyrosine-protein kinase/ Janus kinase-1 (JAK1). The ligand-receptor was performed using AutoDock Vina v1.2.0. The highest extracted tomatidine was found in chloroform at 2.44 % of total alkaloid-steroid, and cannot be found in water. The highest interaction is observed in the SMO-tomatidine interaction complex, followed by JAK-1. Furthermore, physicochemical properties of tomatidine make it invaginated into the hydrophobic side of the target proteins that are mainly triggered by van der Waals and alkyl interaction. Based on the in-silico study, tomatidine significantly interacted in the oncogenic signaling pathways that therapeutically potential inhibit cancer cell proliferation. Further study should be focused on the effectiveness analysis of the SHH signaling pathway in the cancer cell. © 2023, Walailak University. All rights reserved.
Biology Department, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Central Java, 50229, Indonesia; Chemistry Department, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Central Java, 50229, Indonesia; Laboratorium of Biochemistry, Biology Department, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Central Java, 50229, Indonesia; Biotechnology Department, Postgraduate School, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia
