Acacia Honey-derived Bioactive Compounds Exhibit Induction of p53-dependent Apoptosis in the MCF-7 Human Breast Cancer Cell Line

Abstract

Background Research studies have focused on discovering new anti-proliferative and pro-apoptotic agents derived from natural products from which honey constitutes a prominent candidate. The Acacia honey (AH) is known to display anticancer activity, but the mechanisms of action are still not well defined. Objectives Using in vitro and computational approaches, we aimed to assess the interaction among selected bioactive compounds derived from AH, with the apoptotic protein p53, which could trigger apoptosis. Methods The phytocompounds of AH were investigated via gas chromatography–mass spectrophotometry analysis. The cytotoxic effect and induced apoptosis on the MCF-7 breast cancer cell line were assessed by 3-(4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromide and acridine orange-ethidium bromide staining approaches. The molecular docking analysis between AH compounds and p53 was carried out. Results The drug-likeness prediction revealed that most of the identified compounds meet Lipinski’s rules. We demonstrate that AH exerts an interesting cytotoxic effect in a dose-dependent manner against the MCF-7 cell line with IC50 5.053µg/mL. Significant cell alterations and notable induced apoptosis were detected when cells were treated with AH. The molecular docking analysis revealed that melezitose is among the most important potential bioactive compounds that interact with p53 leading to apoptosis. The binding affinity was −8.1 kcal/mol, and the closest molecular interactions in the active site included 10 residues, which could explain the potential biological activity. Conclusion This work sheds light on AH as a significant source of bioactive chemicals with potential for promoting apoptosis that may be exploited as an alternative therapy for breast cancer.

Honey-based therapeutics: a comprehensive review of anticancer, antioxidant, and prognostic impacts in breast cancer treatment

“…30 That finding was also confirmed in another study investigating Acacia honey derived from Saudi Arabia and prominent anticancer activity on same MCF-7 cell line (IC 50 5.053 µg/mL) were noticed with apoptosis inducing essentially(Figure 2). 13 The in silico investigation of Acacia honey compounds disclosed that melezitose is among the most important potential bioactive compounds that could interact with apoptotic p53 protein to trigger apoptosis . 13 Likewise the anticancer effects related to apoptosis inducing have been also demonstrated through its anti-estrogenic effects and its ability to trigger mitochondrial membrane depolarization and apoptosis in breast cancer cells.…”

“…13 The in silico investigation of Acacia honey compounds disclosed that melezitose is among the most important potential bioactive compounds that could interact with apoptotic p53 protein to trigger apoptosis . 13 Likewise the anticancer effects related to apoptosis inducing have been also demonstrated through its anti-estrogenic effects and its ability to trigger mitochondrial membrane depolarization and apoptosis in breast cancer cells. 31 The anti-estrogenic effects have been assigned to polyphenolic honey compounds mainly the Chrysin (5, 7-dihydroxyflavone) which is able to inhibit the aormatase cytochrome P450 enzyme that transform androgens to estrogens.…”

“…This diversity enriches the honey composition with potent properties to cure diseases mainly breast cancer. 12,13 In this review, we report the findings obtained about honey investigation as well honey-based therapeutics in breast cancer considering the last reports from 2020 to 2024 referring to bibliographical data.…”