Effect of Caesalpinia sappan and Annona muricata isolates on VEGF-mediated angiogenesis in HeLa cells

Angiogenesis plays an important role in the growth of cancer cells, including cervical cancer. The compounds in sappan wood (Caesalpinia sappan L.) and soursop leaves (Annona muricata L.) have potential anticancer properties. The objective of this study was to evaluate the effect of sappan wood and soursop leaf isolates on the cytotoxic activity and VEGF expression in HeLa cells. Sappan wood and soursop leaf isolates were obtained by column chromatography, while their characteristics were analyzed by Fourier transform infrared spectroscopy (FTIR) and liquid chromatography-high resolution mass spectrometry (LC-HRMS). The MTT assay was used to detect the cytotoxicity. The expression of VEGF was measured using immunohistochemical staining, while its interaction was studied using network pharmacology and molecular docking. The study identified that sappan wood isolate contains (3-Hydroxybenzyl) malonic acid and (+/-)9-HpODE, while soursop leaf isolate contains (3-Hydroxybenzyl) malonic acid. Molecular docking data indicate that these compounds may suppress angiogenesis activity by inhibiting SRC, AKT1, EGFR, and VEGFR. Isolates of sappan wood and soursop leaves have IC50s of 8.20 and 25.63 µg/ml. A combination of 1/8 sappan wood and 1/10 soursop leaves showed a strong synergistic interaction in causing cell death. VEGF expression in the treated samples was less than in the control cells. Thus, it can be concluded that the single isolate or combination of sappan wood and soursop leaf acts by suppressing VEGF expression and inhibiting the vascularization process.