Anticancer potential of turmeric (Curcuma longa) ethanol extract and prediction of its mechanism through the Akt1 pathway

Abstract

Background: Turmeric (Curcuma longa) has high potential as a traditional anticancer drug. This study aimed to analyze the anticancer activity of turmeric ethanol extract on T47D cells and examine the interaction of Akt1 protein with compounds contained in turmeric. Methods: The cytotoxicity assay was conducted using WST-1 reagents. Apoptosis assay used annexin V-PI, whereas cell cycle assay used PI, and then the results were analyzed using a flow cytometer. LC-HRMS analysis was conducted to identify the active compounds. Docking between Akt1 and ligands was performed using Autodock 4.2 software. Molecular dynamics simulations were conducted using YASARA with a time parameter of 20 ns, pH 7.4, and 37°C. Results: The extract had a strong toxicity on T47D cells (cytotoxicity IC50 value: 26.36 ± 1.55 µg/mL). The extract induced apoptosis of T47D cells at the IC50 dose (~30% cells) and induced the cell cycle arrest in G1 phase. Curcumin, 2-hydroxycinnamic acid and caryophyllene oxide had lower binding energy into Akt1 than AZD5363 used as a positive control. Curcumin, Ar-turmerone, and α-curcumene bind in the ATP binding pocket of Akt1, so the compounds have a high potential to be an ATP-competitive Akt1 inhibitors. The interaction of Akt1 with the compound contained in turmeric had an RMSD backbone value that was more stable than that of ATP and AZD5363. Root-mean-square fluctuation values indicated that amino acid residues that had an essential role in ligand binding sites were stable during simulation. Conclusions: The turmeric ethanol extract had a potential anti-cancer effect by inducing apoptosis and inhibiting cell cycle progression on T47D cells. The docking analysis showed that the active compounds of the extract, such as curcumin, Ar-turmerone, caryophyllene oxide, and α-curcumene, were able to bind into the ATP binding pocket of Akt1 that might inhibit the protein activity and induce cell cycle arrest.