Evaluation of Anticancer Potential of Flavones from Rhamnus alaternus against B16F10 Melanoma Cells

Abstract

Melanoma has become an important health problem and new treatment have become an imperative medical need. Therefore, the finding and identification of natural product with less toxic effects, capable of promoting melanoma cell death have become an important goal of research in oncotherapy. In this study, we want to investigate the anticancer activity of an enriched total oligomers flavonoids (TOF) extract of R. alaternus in melanoma cells. First, TOF was exhibited to be rich in flavones. We revealed that this extract reduced proliferation and increased of sub-G1 and S phase cells built-up in B16-F10 cells in a dose-related manner. Moreover, In Vivo, TOF reduced tumor volume and weight with percentages of inhibition of 92.4% and 92.9%, respectively. R. alaternus was also found to be effective in reducing the level of pro-inflammatory cytokine IL-6 during metastasis. Level of TH1 cytokine, such as IL-2, was significantly enhanced by TOF treatment. Indeed, the histological examination of the tumor revealed the absence of mitoses and the presence of numerous melanin pigmented macrophage cells in the R. alaternus extract-treated group that could be explained by the induction of macrophage activation and by the arrest of the cell cycle in the Sub-G1 and S phases.

The authors acknowledge the ‘‘Ministry of Higher Education, Scientific Research and Technology, Tunisia,” for the support of this study. This work was supported by Research Unit Bioactive Natural Products and Biotechnology, University of Monastir, Tunisia.

Authors’ Contributions

BCI and KY substantially contributed to conception and design, or analysis and data interpretation and drafted the manuscript. MM and LA contributed to the cellular study. GKS, KR and SSSS contributed to the histological examination of the tumor. KM and CGL provided final approval of the version to be published.

Disclosure Statement

We wish to confirm that there are no known conflicts of interest associated with this publication and this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.

Funding

This work was supported by Research Unit Bioactive Natural Products and Biotechnology, University of Monastir, Tunisia.

Data Availability Statement

Address to the authors for the uses of the images and data included in the manuscript.