Adriani SUSANTY, Ihsan IKHTIARUDIN, Mira FEBRINA, Haiyul FADHLI, Rahayu UTAMI, Nurdina PUTRI, Ikhsal Mukri JUMADILA, Fatma Sri WAHYUNI, Dachriyanus DACHRIYANUS
Journal of Research in Pharmacy - 2025;29(6):2643-2669
Voacangine is a mono-indole alkaloid reported to have cytotoxic activity against several cancer cells. This study aimed to explore the ability of voacangine to induce apoptosis and cell cycle arrest on MCF7 through in silico and in vitro studies. The in silico studies were performed through DFT analysis, molecular docking, pharmacokinetic profiling, and toxicity risk prediction. The in vitro apoptosis and cell cycle arrest studies were performed through the flow cytometry Annexin V-FITC/PI. The docking results showed that the apoptosis induction of voacangine was produced mainly through interactions with AKT and PARP, and also interacts with p53, Fas-L, Caspase-8, Cytochrome-C, Caspase-9, and Caspase-3. Voacangine also exhibited the potency for cell cycle arrest mainly through interaction with CDK-2 and CDK-4 and interacts with p53, p21, Cyclin-D, and Cyclin-T. Voacangine exhibited more negative binding free energy than doxorubicin when docked to AKT, PARP, CDK-2, and CDK-4 and its binding energies were close to doxorubicin when docked to other proteins. In addition, voacangine also exhibited considerable pharmacokinetic profiles and toxicity risk as a drug candidate. The in silico studies predicted that voacangine has dual pathways through apoptosis induction via the AKT pathway and cell cycle inhibition, mainly in the G1/S phase. The results of in vitro evaluation are in line with the results of in silico studies that voacangine exhibited the highest total percentage of apoptosis induction (56.8%) and cell cycle arrest dominantly in the G1/S phase. In comparison, doxorubicin only showed apoptosis induction (21.2%) and different pathways on cell cycle arrest (G2/M phase).
