Purification of α-amyrin-acetate and phenylpropanoïd compounds from Ficus umbellata Vahl (Moraceae) stem bark and evaluation of their anti-breast cancer potential

Abstract

Background

Ficus umbellata Vahl is one of the plants used in Cameroonian empirical system to treat cancer. Previous studies have shown its cytotoxic potential on mammary and ovarian cancer cells, and its chemopreventive potential against ovarian cancer in rats. The aim of this work was to determine the bioactive constituents of F. umbellata Vahl and to elucidate the molecular mechanisms of action of the promising one.

Methods

F. umbellata stem bark extract was partitioned and bioguided-fractionation was performed using MTS assay on breast (MDA-MB-231 and MCF-7) and ovarian (Hey, Hey-Cis, PA-1 and OAW-42) cancer cell lines. Further, isolates were purified, characterized and tested. The most active compound was investigated on cell growth, cell proliferation, formation of clones, cell death mechanisms, caspase-3 activity, wound healing, chemotaxis and cell adhesion. Moreover, the expression of proteins related to epithelial-to-mesenchymal transition (EMT), apoptosis and MAP-kinase were also measured using Western blot.

Results

Out of the 4 isolates, C1 (α-amyrin-acetate) had significant cytotoxic potential on MDA-MB-231 (∼10 μg/mL), Hey-Cis (10.59) and PA-1 (13.18 μg/mL). Further, it reduced MDA-MB 231 cell growth (p ˂ 0.01) and proliferation (p ˂ 0.05), as well as clone formation (p ˂0.001) at 10 µg/mL. C1 increased the number of apoptotic cells by 50 % at 5 µg/mL and 65 % at 10 µg/mL, accompanied by an increase (p ˂ 0.05) in caspase-3 activity. It inhibited cell migration/invasion (p ˂ 0.01) and increased their adherence to collagen and fibronectin. It promoted the cleavage of Poly (ADP-ribose) polymerase, increased E-cadherin, and significantly (p ˂ 0.01) inhibited both vimentin and phosphorylated extracellular signal-regulated activation.

Conclusion

In sum α-amyrin-acetate is at least partly responsible for F. umbellata cytotoxic effect mediated through proapoptotic response and protection against Epithelial-to-mesenchymal transition.