Breast cancer cell growth arrest and chemopreventive effects of Passiflora edulis Sims (Passifloraceae) ethanolic leaves extract on a rat model of mammary carcinoma

Ethnopharmacological relevance: Despite various prevention and treatment measures, the incidence and mortality due to breast cancer has been increasing globally. Passiflora edulis Sims is a plant used for the treatment of various diseases in traditional medicine, including cancers. Aim of the study: To assess the anti-breast cancer activity of the ethanolic extract of P. edulis leaves in vitro and in vivo. Material and methods: In vitro, the cell growth and proliferation were determined based on the MTT and BrdU assays. The flow cytometry was used to analyze the cell death mechanism while, cell migration, cell adhesion and chemotaxis were assayed for anti-metastatic potential. In vivo, 56 female Wistar rats aged 45-50 days (similar to 75 g) were exposed to 7,12-dimethylbenz(a)anthracene-DMBA except the normal group. Negative control group (DMBA) received solvent dilution throughout the study; standards groups (tamoxifen -3.3 mg/kg BW and letrozole -1 mg/kg BW) as well as P. edulis leaves ethanolic extract groups (50, 100 and 200 mg/kg) treated for 20 weeks. Tumor incidence, tumor burden and volume, CA 15-3 serum' level, antioxidant, inflammatory status and histopathology were assessed. Results: P. edulis extract showed a significant and concentration-dependent inhibition of MCF-7 and MDA-MB 231 cells growth at 100 mu g/mL. It inhibited cell proliferation and clones' formation and induced apoptosis in MDA-MB 231 cells. The migration of cell into the zone freed of cells and the number of invading cells after the 48 and 72 h were significantly diminished while, it increased their adherence to collagen and fibronectin extra -cellular matrix as does Doxorubicin. In vivo, all rats in the DMBA group exhibited a significant (p < 0.001) increase in tumor volume, tumor burden and grade (adenocarcinoma of SBR III) and pro-inflammatory cytokine levels (TNF-alpha, INF-gamma, IL-6 and IL-12). P. edulis extract at all tested doses significantly inhibited the DMBA-induced increase in tumor incidence, tumor burden and grade (SBR I) as well as pro-inflammatory cytokines. Moreover, it increased enzymatic and non-enzymatic antioxidants (SOD, catalase, and GSH) and decreased MDA levels although a greater effect was observed with Tamoxifen and Letrozole. P. edulis has medium content on polyphenols, flavonoids and tannins. Conclusion: P. edulis has chemo-preventive effects against DMBA-induced breast cancer in rats probably through its antioxidative, anti-inflammatory and apoptosis-inducing potentials.