The Potency Anticancer Candidate of Trisindolina 1 with In vitro and In Silico Methods

Cancer can arise from the malignant transformation of normal cells due to carcinogenic induction that damages DNA and disrupts the cell cycle. DNA damage is corrected in the G1 phase of the cell cycle by expression and activation of the p53 tumor suppressor. The prominent outcomes of p53 activation are cycle arrest and apoptosis. Therefore, p53 is used as a target for anticancer drug development. Hyperactivation or deregulation of the MAPK (mitogen activated protein kinase) pathway can affect liver cancer. MAPK activation plays an important role in regulating inflammation associated with cancer development. Therefore, MAPK is considered as a therapeutic target. Trisindoline 1 is a natural compound that has previously been shown to have high cytotoxic effect on HepG2 cells. This study aims to decide the potential of trisindoline 1 as an anticancer drug for HepG2 liver cancer cell line and to decide the activity of trisindoline 1 with the MAPK pathway targeting HepG2 cancer through in silico analysis. Molecular docking was performed on trisindoline 1 against ERK1, JNK2 and p38 proteins in the MAPK pathway. Pharmacokinetic and physicochemical analysis were carried out using SwissADME for evaluation of drug-likeness. Cell proliferation was analysed using the MTT assay method. Trisindoline 1 showed high cytotoxic activity against HepG2 with an IC50 value of 2.837 μg/ml and showed low toxicity against Vero cells. Based on the analysis of physicochemical properties, trisindoline 1 met the properties of drug-likeness and has lower toxicity compared to Doxorubicin. The docking results show that trisindoline 1 has the potential to be an inhibitor of the ERK2, JNK1 and p38 MAPK pathways. These results suggest that trisindoline 1 has the potential as an anticancer drug.