Engl. & Diels (Annonaceae) inhibitory and cytotoxic effects on breast adenocarcinoma growth both and .

Background: Breast cancer is ranked as the most common malignant tumor in women globally with ∼ 2.3 million new cases (11.7 %) diagnosed in 2020. The multiple drawbacks associated with treatments, prompt researchers and patients to search for alternative therapy. Plants continue to offer encouraging leads, in particular those of the Annonaceae family, to which belongs used by Cameroonian traditional healers to fight cancers. This study was aimed at investigating the effect of against human breast cancer cells. This was carried out by investigating the cytotoxicity, underlying mechanism of action and chemopreventive potential of on 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer.

Methods: To achieve this goal, the ethanolic extract of the bark of was prepared and assayed for its ability to inhibit cell growth, cell proliferation and clone formation. Furthermore, cell death mechanisms, cell cycle progression and anti-metastatic potential were investigated. The study consisted in a once-off administration of 50 mg/kg BW DMBA (in olive oil, ) from the 10th day after pretreatment with extract (50 and 100 mg/kg BW) or standards [tamoxifen (3.3 mg/kg) and letrozole (1 mg/kg)] or leaf extract of L. (200 mg/kg as pharmacological control). Normal and negative controls received vehicle (3 % ethanol). The treatment of animals was done for 20 weeks, followed by the assessment of the incidence, burden and volume of tumors, breast cancer biomarker (CA 15-3), antioxidant status, inflammatory status and histopathology profile. The LD of extract was estimated according to OECD guideline 423.

Results: displayed cytotoxicity at 80 μg/mL on all the tested breast cancer cell lines. It induced apoptosis and caused a blockade at G0/G1; S-phase of MDA-MB 231 cells, thus, suggesting anticancer potential. A significant concentration-dependent antimetastatic potential was observed with extract at 50 ( < 0.05) and 100 ( < 0.01) μg/mL, evidenced by a reduction in cell migration, chemotaxis and increased adhesion to extracellular matrix. With respect to the chemopreventive study, was able to prevent the onset of breast adenocarcinoma in Wistar rats by preventing the growth of tumor mass and volume, as well as the histopathological severity of the disease. This was achieved through the modulation of antioxidant parameters (SOD, CAT, MDA) and inflammatory parameters (IL-12, IL-6, INF- gamma, TNF). Also, the LD of extract was greater than 2000 mg/kg, indicating low acute toxicity and thus, favorable for therapeutic use.

Conclusion: In summary, this study outlines for the first time the beneficial effect of as a plant candidate in the fight against breast cancer just like other species of the Annonaceae family. However, further research studies are still warranted regarding its bioactive components, and in depth investigation of its anticancer mechanism of action are also needed.