Apoptosis and cell cycle regulatory of voacangine ısolated from Voacanga foetida (Blume) Rolfe on MCF7 breast cancer cells: In silico and in vitro studies

Year 2025, Volume: 29 Issue: 6, 2643 - 2669, 02.11.2025

Adriani Susanty Ihsan Ikhtiarudin , Mira Febrina Haiyul Fadhlı Rahayu Utami Nurdina Putri Ikhsal Mukri Jumadila Fatma Sri Wahyuni Dachriyanus Hamidi

https://doi.org/10.12991/jrespharm.1798462

Abstract

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).

Keywords

Voacangine , apoptosis , cell cycle , Voacanga foetida , MCF7

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