Flavonoids Overcome Drug Resistance to Cancer Chemotherapy by Epigenetically Modulating Multiple Mechanisms
- 1 April 2021
- journal article
- review article
- Published by Bentham Science Publishers Ltd. in Current Cancer Drug Targets
- Vol. 21 (4), 289-305
- https://doi.org/10.2174/1568009621666210203111220
Abstract
Drug resistance is the major reason accounting for the treatment failure in cancer chemotherapy. Dysregulation of the epigenetic machineries is known to induce chemoresistance. It was reported that numerous genes encoding the key mediators in cancer proliferation, apoptosis, DNA repair, and drug efflux are dysregulated in resistant cancer cells by aberrant DNA methylation. The imbalance of various enzymes catalyzing histone post-translational modifications is also known to alter chromatin configuration and regulate multiple drug resistance genes. Alteration in miRNA signature in cancer cells also gives rise to chemoresistance. Flavonoids are a large group of naturally occurring polyphenolic compounds ubiquitously found in plants, fruits, vegetables and traditional herbs. There has been increasing research interest in the health-promoting effects of flavonoids. Flavonoids were shown to directly kill or re-sensitize resistant cancer cells to conventional anticancer drugs by epigenetic mechanisms. In this review, we summarize the current findings of the circumvention of drug resistance by flavonoids through correcting the aberrant epigenetic regulation of multiple resistance mechanisms. More investigations including the evaluation of synergistic anticancer activity, dosing sequence effect, toxicity in normal cells, and animal studies, are warranted to establish the full potential of the combination of flavonoids with conventional chemotherapeutic drugs in the treatment of cancer with drug resistance.Keywords
Funding Information
- Chinese University of Hong Kong (4054497)
- Food and Health Bureau (7180316)
This publication has 143 references indexed in Scilit:
- Stilbene derivatives promote Ago2-dependent tumour-suppressive microRNA activityScientific Reports, 2012
- A Peek into the Complex Realm of Histone PhosphorylationMolecular and Cellular Biology, 2011
- (-)-Epigallocatechin-3-gallate and DZNep reduce polycomb protein level via a proteasome-dependent mechanism in skin cancer cellsCarcinogenesis: Integrative Cancer Research, 2011
- Pro-oxidative activities and dose–response relationship of (−)-epigallocatechin-3-gallate in the inhibition of lung cancer cell growth: a comparative study in vivo and in vitroCarcinogenesis: Integrative Cancer Research, 2010
- Laboratory correlates for a phase II trial of romidepsin in cutaneous and peripheral T-cell lymphomaBritish Journal of Haematology, 2009
- HDAC expression and clinical prognosis in human malignanciesCancer Letters, 2009
- Oxidative response gene polymorphisms and risk of adult brain tumorsNeuro-Oncology, 2008
- TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencingNature, 2005
- Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespanNature, 2003
- Translating the Histone CodeScience, 2001