title: Genistein and cancer: current status, challenges, and future directions.
abstract: Primary prevention through lifestyle interventions is a cost-effective alternative for preventing a large burden of chronic and degenerative diseases, including cancer, which is one of the leading causes of morbidity and mortality worldwide. In the past decade, epidemiologic and preclinical evidence suggested that polyphenolic phytochemicals present in many plant foods possess chemopreventive properties against several cancer forms. Thus, there has been increasing interest in the potential cancer chemopreventive agents obtained from natural sources, such as polyphenols, that may represent a new, affordable approach to curb the increasing burden of cancer throughout the world. Several epidemiologic studies showed a relation between a soy-rich diet and cancer prevention, which was attributed to the presence of a phenolic compound, genistein, present in soy-based foods. Genistein acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. Targeting caspases, B cell lymphoma 2 (Bcl-2)-associated X protein (Bax), Bcl-2, kinesin-like protein 20A (KIF20A), extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear transcription factor κB (NF-κB), mitogen-activated protein kinase (MAPK), inhibitor of NF-κB (IκB), Wingless and integration 1 β-catenin (Wnt/β-catenin), and phosphoinositide 3 kinase/Akt (PI3K/Akt) signaling pathways may act as the molecular mechanisms of the anticancer, therapeutic effects of genistein. Genistein also shows synergistic behavior with well-known anticancer drugs, such as adriamycin, docetaxel, and tamoxifen, suggesting a potential role in combination therapy. This review critically analyzes the available literature on the therapeutic role of genistein on different types of cancer, focusing on its chemical features, plant food sources, bioavailability, and safety.
authors.affiliation: Institute of Food Sciences, National Research Council, Avellino, Italy;
authors.forename: Carmela
authors.initials: C
authors.lastname: Spagnuolo
authors.affiliation: Institute of Food Sciences, National Research Council, Avellino, Italy; glrusso@isa.cnr.it.
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Russo
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, Turkey;
authors.forename: Ilkay Erdogan
authors.initials: IE
authors.lastname: Orhan
authors.affiliation: Pharmacognosy Research Laboratories, Medway School of Science, University of Greenwich, Chatham-Maritime, United Kingdom;
authors.forename: Solomon
authors.initials: S
authors.lastname: Habtemariam
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Pavia, Italy;
authors.forename: Maria
authors.initials: M
authors.lastname: Daglia
authors.affiliation: Research Group on Community Nutrition and Oxidative Stress and CIBERobn (Physiopathology of Obesity and Nutrition), University of Balearic Islands, Palma de Mallorca, Spain;
authors.forename: Antoni
authors.initials: A
authors.lastname: Sureda
authors.affiliation: Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;
authors.forename: Seyed Fazel
authors.initials: SF
authors.lastname: Nabavi
authors.affiliation: Department of Biotechnology, Alagappa University, Karaikudi, Tamil Nadu, India; and.
authors.forename: Kasi Pandima
authors.initials: KP
authors.lastname: Devi
authors.affiliation: Department of Pharmacy, Health, and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Monica Rosa
authors.initials: MR
authors.lastname: Loizzo
authors.affiliation: Department of Pharmacy, Health, and Nutritional Sciences, University of Calabria, Rende, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Tundis
authors.affiliation: Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran; glrusso@isa.cnr.it.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Nabavi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D061945:Caspase Inhibitors; D020169:Caspases; D002453:Cell Cycle / Q000187:drug effects; D018890:Chemoprevention; D004357:Drug Synergism; D007887:Fabaceae; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009369:Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D064209:Phytochemicals; D045730:Soy Foods; D013025:Glycine max
chemical_list: D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D064209:Phytochemicals; D019833:Genistein; D020169:Caspases
keywords: bioavailability; cancer; genistein; safety; source