Phenolic compounds as Nrf2 inhibitors: potential applications in cancer therapy

Javad Sharifi-Rad; Veronique Seidel; Michalak Izabela; Margalida Monserrat-Mequida; Antoni Sureda; Valeska Ormazabal; Felipe A Zuniga; Shivaprasad Shetty Mangalpady; Raffaele Pezzani; Alibek Ydyrys; Gulmira Tussupbekova; Miquel Martorell; Daniela Calina; William C Cho

doi:10.1186/s12964-023-01109-0

Phenolic compounds as Nrf2 inhibitors: potential applications in cancer therapy

Cell Commun Signal. 2023 May 1;21(1):89. doi: 10.1186/s12964-023-01109-0.

Authors

Javad Sharifi-Rad¹, Veronique Seidel², Michalak Izabela³, Margalida Monserrat-Mequida^{4

5

6}, Antoni Sureda^{4

5

6}, Valeska Ormazabal⁷, Felipe A Zuniga⁸, Shivaprasad Shetty Mangalpady⁹, Raffaele Pezzani^{10

11}, Alibek Ydyrys^{12

13}, Gulmira Tussupbekova¹⁴, Miquel Martorell^{15

16}, Daniela Calina¹⁷, William C Cho¹⁸

Affiliations

¹ Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador. javad.sharifirad@gmail.com.
² Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
³ Department of Advanced Material Technologies, Faculty of Chemistry, Wroclaw University of Science and Technology, Smoluchowskiego 25, 50-372, Wroclaw, Poland.
⁴ Research Group in Community Nutrition and Oxidative Stress, University of the Balearic Islands-IUNICS, 07122, Palma, Spain.
⁵ Health Research Institute of Balearic Islands (IdISBa), 07120, Palma, Spain.
⁶ CIBER Fisiopatología de La Obesidad Y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain.
⁷ Department of Pharmacology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
⁸ Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile.
⁹ Department of Chemistry, NMAM Institute of Technology, Nitte, Karnataka, 574110, India.
¹⁰ Phytotherapy Lab, Endocrinology Unit, Department of Medicine (DIMED), University of Padova, Via Ospedale 105, 35128, Padova, Italy.
¹¹ AIROB, Associazione Italiana Per La Ricerca Oncologica Di Base, Padova, Italy.
¹² Biomedical Research Centre, Al-Farabi Kazakh National University, Al-Farabi Ave. 71, 050040, Almaty, Kazakhstan.
¹³ The Elliott School of International Affairs, 1957 E St NW, George Washington UniversityWashington DC, 20052, USA.
¹⁴ Department of Biophysics, Biomedicine and Neuroscience, Al-Farabi Kazakh National University, Al-Farabi Ave. 71, 050040, Almaty, Kazakhstan.
¹⁵ Department of Nutrition and Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, Concepción, Chile. mmartorell@udec.cl.
¹⁶ Universidad de Concepción, Unidad de Desarrollo Tecnológico, UDT, 4070386, Concepción, Chile. mmartorell@udec.cl.
¹⁷ Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania. calinadaniela@gmail.com.
¹⁸ Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong. chocs@ha.org.hk.

Abstract

Cancer is a leading cause of death worldwide and involves an oxidative stress mechanism. The transcription factor Nrf2 has a crucial role in cytoprotective response against oxidative stress, including cancer growth and progression and therapy resistance. For this reason, inhibitors of Nrf2 are new targets to be studied. Traditional plant-based remedies rich in phytochemicals have been used against human cancers and phenolic compounds are known for their chemopreventive properties. This comprehensive review offers an updated review of the role of phenolic compounds as anticancer agents due to their action on Nrf2 inhibition. In addition, the role of naturally-occurring bioactive anticancer agents are covered in the clinical applications of polyphenols as Nrf2 inhibitors. Video Abstract.

Keywords: Apoptosis; Cancer; Cytotoxicity; Nrf2; Oxidative stress; Phenolic compounds.

Publication types

Video-Audio Media
Review
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / pharmacology
Antioxidants / metabolism
Humans
NF-E2-Related Factor 2 / metabolism
Neoplasms* / drug therapy
Oxidative Stress
Phenols / pharmacology
Phenols / therapeutic use

Substances

NF-E2-Related Factor 2
Antineoplastic Agents
Antioxidants
Phenols