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

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 i...

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Main Author:	Banik, Urmila
Format:	Thesis
Language:	English
Published:	2023
Subjects:	R Medicine
Online Access:	http://eprints.usm.my/60005/1/URMILA%20BANIK-FINAL%20THESIS%20S-UD000616%28R%29%20-E.pdf
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spelling	my-usm-ep.600052024-03-19T07:03:17Z Understanding the cellular and molecular mechanism of anticancer effect of tualang honey on breast cancer in vivo and in vitro model 2023-09 Banik, Urmila R Medicine RC254-282 Neoplasms. Tumors. Oncology (including Cancer) RV Botanic, Thomsonian, and eclectic medicine 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. 2023-09 Thesis http://eprints.usm.my/60005/ http://eprints.usm.my/60005/1/URMILA%20BANIK-FINAL%20THESIS%20S-UD000616%28R%29%20-E.pdf application/pdf en public phd doctoral Universiti Sains Malaysia Pusat Pengajian Sains Perubatan
institution	Universiti Sains Malaysia
collection	USM Institutional Repository
language	English
topic	R Medicine R Medicine R Medicine
spellingShingle	R Medicine R Medicine R Medicine Banik, Urmila Understanding the cellular and molecular mechanism of anticancer effect of tualang honey on breast cancer in vivo and in vitro model
description	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.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Banik, Urmila
author_facet	Banik, Urmila
author_sort	Banik, Urmila
title	Understanding the cellular and molecular mechanism of anticancer effect of tualang honey on breast cancer in vivo and in vitro model
title_short	Understanding the cellular and molecular mechanism of anticancer effect of tualang honey on breast cancer in vivo and in vitro model
title_full	Understanding the cellular and molecular mechanism of anticancer effect of tualang honey on breast cancer in vivo and in vitro model
title_fullStr	Understanding the cellular and molecular mechanism of anticancer effect of tualang honey on breast cancer in vivo and in vitro model
title_full_unstemmed	Understanding the cellular and molecular mechanism of anticancer effect of tualang honey on breast cancer in vivo and in vitro model
title_sort	understanding the cellular and molecular mechanism of anticancer effect of tualang honey on breast cancer in vivo and in vitro model
granting_institution	Universiti Sains Malaysia
granting_department	Pusat Pengajian Sains Perubatan
publishDate	2023
url	http://eprints.usm.my/60005/1/URMILA%20BANIK-FINAL%20THESIS%20S-UD000616%28R%29%20-E.pdf
_version_	1794024075725635584

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

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