Understanding the cellular and molecular mechanism of anticancer effect of tualang honey on breast cancer in vivo and in vitro model

• Main Author: Banik, Urmila
• Format: Thesis
• Language: English
• Published: 2023
• Subjects: R Medicine; RC254-282 Neoplasms. Tumors. Oncology (including Cancer); RV Botanic, Thomsonian, and eclectic medicine
• Online Access: http://eprints.usm.my/60005/1/URMILA%20BANIK-FINAL%20THESIS%20S-UD000616%28R%29%20-E.pdf; http://eprints.usm.my/60005/

Honey is a natural product (NP) that has become a significant option in breast cancer (BC) treatment. It has been shown to possess substantial anticancer properties, but the mechanism of action remains unclear. Therefore, this study was undertaken to explore honey's anticancer effect on BC in vivo and in vitro in relation to its ability to enhance apoptosis, modulate cell cycle progression, and regulate microRNA expression. Histomorphological effect of Tualang honey (TH) and Manuka honey on MNU-induced BC of female Sprague Dawley rats were studied by analysing archival routine histopathology slides with light microscope. Subsequently, considering the anticancer potentiality of TH in vitro, analysis was done on MCF-7 BC cells. TH was diluted in a final concentration of 2%, 3%, 3.5% and 4% (v/v). MCF-7 cells were treated with TH. Untreated MCF-7 cells served as a control. Apoptosis and cell cycle were studied by flow cytometry. Small RNA sequencing was done, using NGS Illumina platform to analyse possible modulation of miRNA expression by TH. The effect of TH was compared with that of the anticancer drug Doxorubicin (0.5micromolar; DOX). Histomorphologically, honey treatment on MNU-induced BC in SD rat models resulted in a lower histological grade, less necrosis but increased in cytoplasmic vacuolisation compared to non-treated; implicating positive anticancer efficacy of honey. TH treatment in MCF-7 cells resulted in increased cell fraction in G2/M with reduced cell fraction in the S phase, dose-dependent increased cytotoxicity, and enhanced apoptosis. TH-induced cytological changes, proapoptotic and cell cycle modulatory effect showed similarity with that of DOX treatment. One hundred miRNAs were differentially expressed; 63 were upregulated (UR), and 37 were downregulated (DR). Nineteen DE miRNAs were common in three concentrations of TH. Most DE miRNAs of DOX treatment were also expressed with TH treatment. Upregulation of miR-129-5p, miR-139-5p, miR-215-5p, miR-184 & miR-574-5p; downregulation of miR-182-5p, miR-103a-3p & miR-191-5p attests to antiproliferative, cell cycle modulatory, the proapoptotic effect of TH. KEGG pathway analysis showed that multiple pathways related to apoptosis, cell proliferation, cell growth, survival and cell cycle progression are important targeted pathways by THmodulated miRNAs. Honey may exert an antitumor effect by interfering with miRNAs in BC cells. The study reveals a novel role for honey in inhibiting BC progression by modulating miRNAs, thereby affecting the cell cycle and apoptosis.