Polyphenol-enriched fraction of Acacia seyal Delile (Mimosaceae) inhibits human triple-negative breast cancer cells and exhibits anticancer and immunomodulatory effects in a DMBA-induced breast cancer model.

INTRODUCTION

Breast cancer killed 665,684 patients globally in 2022 despite government efforts and conventional therapies. The hydro-ethanolic extract of Acacia seyal, a sub-Saharan African ethnomedicinal plant, showed moderate cytotoxicity, significant anti-migration and in vivo preventive effects against breast cancer cells. The aim of this study was to propose an improved traditional extract and to evaluate its efficacy and potential mechanism of action.

METHODS

To achieve this, A. seyal hydro-ethanolic extract (ASHE) was fractionated in polyphenol-enriched (ASpo), polysaccharides (ASsu) and residue (ASre) fractions. Fractions along with the crude extract were tested for their ability to inhibit cell growth (MTT) and proliferation (CCK-8). The promising fraction (ASpo) was further investigated on clone formation, caspase-3, wound healing, chemotaxis and cell adhesion to understand its underlying mechanisms of action. Moreover, ASpo at 18.75 and 37.5 mg/kg, p.o compared to standard drugs (tamoxifen and letrozole) and control (distilled water) were assessed in a 20-week preventive study of DMBA (50 mg/kg, s.c)-induced breast cancer by considering tumor incidence, tumor volume, organ mass, histopathological, hematological, antioxidant and anti-inflammatory/immunomodulatory markers.

RESULTS

Among the 3 fractions, ASpo compared to control, inhibited (p < 0.01) MDA-MB 231 cells growth, proliferation and clone formation at 50 μg/mL. It increased caspase-3 and inhibited cell migration and invasion (p < 0.01) with increase (p < 0.01) adherence to collagen and fibronectin. In vivo, comparable to reference drugs, ASpo reduced tumor incidence (50%), and tumor volume from 7827.30 mm3 (adenocarcinoma SBRIII, 10% lymphocytes infiltration) in DMBA to 804.32 mm3 (adenocarcinoma SBRII, 30% lymphocytes infiltration) at 37.5 mg/kg. It increased femur and thymus'mass, lymphocytes and monocyte levels (p < 0.001) in serum, reduced (p < 0.001) TNF-α, IL-6, IL-12, EGF, nitrites levels whereas increased SOD, catalase and major IFN-γ cytokine (p < 0.001). ASpo additionally showed a safety profile on toxicity organs.

CONCLUSION

Overall, ASpo mainly contributed to anti-breast cancer activities of total crude extract and involved immunomodulatory effects to consider with optimized bioactivity to further investigate it as a promising natural and inexpensive alternative to costly and efficient current immunotherapy.