Evaluation of anti-cancer and anti-inflammatory properties of Crescentia cujete L. and Citrullus vulgaris schrad. methanol seed extracts against MCF-7 breast cancer cells and molecular docking

Abstract

Breast cancer continues to be the leading form of cancer in women all over the world and one of the primary cancer killers of women. Crescentia cujete L. and Citrullus vulgaris Schrad. have longstanding uses in traditional medicine. This study was carried out to determine the anti-inflammatory and anti-cancer characteristics of the methanol extracts of seeds of C. cujete and C. vulgaris. The anti-cancer effects were tested on MCF-7 cells with MTT assay, Annexin V-FITC/PI staining, and cytokine quantification. The anti-inflammatory activity was evaluated using carrageenan and nitric-oxide induced rat model. Both extracts reduced cell viability in a dose dependent manner, showing an IC₅₀ value of 24.5 ± 2.4 µg/mL for C. cujete and 12.6 ± 3.1 µg/mL for C. vulgaris. Flow cytometric analysis provided fluorescence images of MCF-7 cells containing both early and late apoptotic populations. The 200 µg/mL C. cujete treatment yielded an increase in MCF-7 cell apoptosis to 38.2% apoptosis compared to 42.16% for C. vulgaris and 14.24% for doxorubicin whereas the control was at 5.4%. ELISA quantification proved significant TNF-α diminishment along with the IL-1β, and IL-6 levels (p < 0.05). Carrageenan-induced paw edema and nitric oxide (NO) assays in Wistar rats were used to evaluate the in vivo anti-inflammatory activity. At 400 mg/kg, C. Cujete and C. vulgaris extracts, as opposed to 69.1% with Ibuprofen, decreased the volume of paw edema by 61.3% and 47.9%, respectively, at the fifth hour. Serum NO levels were significantly suppressed by 52.6% (C. cujete) and 41.8% (C. vulgaris). Strong binding affinities with important cancer-related targets, such as COX-2 (−9.1 kcal/mol), Bcl-2 (−8.4 kcal/mol), and EGFR (−7.6 kcal/mol), were demonstrated by molecular docking of identified phytochemicals (such as β-sitosterol and cucurbitacin B). The study showed that these plants’ extracts possessed potential anti-cancer and anti-inflammation activities.