Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

Breast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more...

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Autores principales:	Kah Min Yap, Mahendran Sekar, Yuan Seng Wu, Siew Hua Gan, Nur Najihah Izzati Mat Rani, Lay Jing Seow, Vetriselvan Subramaniyan, Neeraj Kumar Fuloria, Shivkanya Fuloria, Pei Teng Lum
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Bioavailability Biosafety Breast cancer Hesperetin Hesperidin Nanoformulation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/25a96a6e475044f896c9328568a908ee
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spelling	oai:doaj.org-article:25a96a6e475044f896c9328568a908ee2021-11-20T04:56:22ZHesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects1319-562X10.1016/j.sjbs.2021.07.046https://doaj.org/article/25a96a6e475044f896c9328568a908ee2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1319562X21006288https://doaj.org/toc/1319-562XBreast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more effective anti-cancer agents. Hesperidin and its aglycone hesperetin, two flavonoids from citrus species, have been extensively evaluated for their anti-cancer potentials. In this review, available literatures on the chemotherapeutic and chemosensitising activities of hesperidin and hesperetin in preclinical BC models are reported. The safety and bioavailability of hesperidin and hesperetin as well as the strategies to enhance their bioavailability are also discussed. Overall, hesperidin and hesperetin can inhibit cell proliferation, migration and BC stem cells as well as induce apoptosis and cell cycle arrest in vitro. They can also inhibit tumour growth, metastasis and neoplastic changes in tissue architecture in vivo. Moreover, the co-administration of hesperidin or hesperetin with doxorubicin, letrozole or tamoxifen can enhance the efficacies of these clinically available agents. These chemotherapeutic and chemosensitising activities of hesperidin and hesperetin have been linked to several mechanisms, including the modulation of signalling pathways, glucose uptake, enzymes, miRNA expression, oxidative status, cell cycle regulatory proteins, tumour suppressor p53, plasma and liver lipid profiles as well as DNA repair mechanisms. However, poor water solubility, extensive phase II metabolism and apical efflux have posed limitations to the bioavailability of hesperidin and hesperetin. Various strategies for bioavailability enhancement have been studied, including the utilisation of nano-based drug delivery systems and the co-administration of hesperetin with other flavonoids. In particular, nanoformulated hesperidin and hesperetin possess greater chemotherapeutic and chemosensitising activities than free compounds. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment.Kah Min YapMahendran SekarYuan Seng WuSiew Hua GanNur Najihah Izzati Mat RaniLay Jing SeowVetriselvan SubramaniyanNeeraj Kumar FuloriaShivkanya FuloriaPei Teng LumElsevierarticleBioavailabilityBiosafetyBreast cancerHesperetinHesperidinNanoformulationBiology (General)QH301-705.5ENSaudi Journal of Biological Sciences, Vol 28, Iss 12, Pp 6730-6747 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bioavailability Biosafety Breast cancer Hesperetin Hesperidin Nanoformulation Biology (General) QH301-705.5
spellingShingle	Bioavailability Biosafety Breast cancer Hesperetin Hesperidin Nanoformulation Biology (General) QH301-705.5 Kah Min Yap Mahendran Sekar Yuan Seng Wu Siew Hua Gan Nur Najihah Izzati Mat Rani Lay Jing Seow Vetriselvan Subramaniyan Neeraj Kumar Fuloria Shivkanya Fuloria Pei Teng Lum Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects
description	Breast cancer (BC) has high incidence and mortality rates, making it a major global health issue. BC treatment has been challenging due to the presence of drug resistance and the limited availability of therapeutic options for triple-negative and metastatic BC, thereby urging the exploration of more effective anti-cancer agents. Hesperidin and its aglycone hesperetin, two flavonoids from citrus species, have been extensively evaluated for their anti-cancer potentials. In this review, available literatures on the chemotherapeutic and chemosensitising activities of hesperidin and hesperetin in preclinical BC models are reported. The safety and bioavailability of hesperidin and hesperetin as well as the strategies to enhance their bioavailability are also discussed. Overall, hesperidin and hesperetin can inhibit cell proliferation, migration and BC stem cells as well as induce apoptosis and cell cycle arrest in vitro. They can also inhibit tumour growth, metastasis and neoplastic changes in tissue architecture in vivo. Moreover, the co-administration of hesperidin or hesperetin with doxorubicin, letrozole or tamoxifen can enhance the efficacies of these clinically available agents. These chemotherapeutic and chemosensitising activities of hesperidin and hesperetin have been linked to several mechanisms, including the modulation of signalling pathways, glucose uptake, enzymes, miRNA expression, oxidative status, cell cycle regulatory proteins, tumour suppressor p53, plasma and liver lipid profiles as well as DNA repair mechanisms. However, poor water solubility, extensive phase II metabolism and apical efflux have posed limitations to the bioavailability of hesperidin and hesperetin. Various strategies for bioavailability enhancement have been studied, including the utilisation of nano-based drug delivery systems and the co-administration of hesperetin with other flavonoids. In particular, nanoformulated hesperidin and hesperetin possess greater chemotherapeutic and chemosensitising activities than free compounds. Despite promising preclinical results, further safety and efficacy evaluation of hesperidin and hesperetin as well as their nanoformulations in clinical trials is required to ascertain their potentials to be developed as clinically useful agents for BC treatment.
format	article
author	Kah Min Yap Mahendran Sekar Yuan Seng Wu Siew Hua Gan Nur Najihah Izzati Mat Rani Lay Jing Seow Vetriselvan Subramaniyan Neeraj Kumar Fuloria Shivkanya Fuloria Pei Teng Lum
author_facet	Kah Min Yap Mahendran Sekar Yuan Seng Wu Siew Hua Gan Nur Najihah Izzati Mat Rani Lay Jing Seow Vetriselvan Subramaniyan Neeraj Kumar Fuloria Shivkanya Fuloria Pei Teng Lum
author_sort	Kah Min Yap
title	Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects
title_short	Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects
title_full	Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects
title_fullStr	Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects
title_full_unstemmed	Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects
title_sort	hesperidin and its aglycone hesperetin in breast cancer therapy: a review of recent developments and future prospects
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/25a96a6e475044f896c9328568a908ee
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Hesperidin and its aglycone hesperetin in breast cancer therapy: A review of recent developments and future prospects

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