Nobiletin in Cancer Therapy: How This Plant Derived-Natural Compound Targets Various Oncogene and Onco-Suppressor Pathways
Milad Ashrafizadeh,
Ali Zarrabi,
Sedigheh Saberifar,
Farid Hashemi,
Kiavash Hushmandi,
Fardin Hashemi,
Ebrahim Rahmani Moghadam,
Reza Mohammadinejad,
Masoud Najafi,
Manoj Garg
Affiliations
Milad Ashrafizadeh
Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran
Ali Zarrabi
Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, Istanbul 34956, Turkey
Sedigheh Saberifar
Department of Basic Sciences, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz 6135783151, Iran
Farid Hashemi
DVM. Graduated, Young Researcher and Elite Club, Kazerun Branch, Islamic Azad University, Kazeroon 7319846451, Iran
Kiavash Hushmandi
Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417414418, Iran
Fardin Hashemi
Student Research Committee, Department of Physiotherapy, Faculty of Rehabilitation, Ahvaz Jundishapur University of Medical Sciences, Ahvaz 6135715749, Iran
Ebrahim Rahmani Moghadam
Student Research Committee, Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
Reza Mohammadinejad
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 7619813159, Iran
Masoud Najafi
Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran
Manoj Garg
Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sector-125, Noida-201313, India
Cancer therapy is a growing field, and annually, a high number of research is performed to develop novel antitumor drugs. Attempts to find new antitumor drugs continue, since cancer cells are able to acquire resistance to conventional drugs. Natural chemicals can be considered as promising candidates in the field of cancer therapy due to their multiple-targeting capability. The nobiletin (NOB) is a ubiquitous flavone isolated from Citrus fruits. The NOB has a variety of pharmacological activities, such as antidiabetes, antioxidant, anti-inflammatory, hepatoprotective, and neuroprotective. Among them, the antitumor activity of NOB has been under attention over recent years. In this review, we comprehensively describe the efficacy of NOB in cancer therapy. NOB induces apoptosis and cell cycle arrest in cancer cells. It can suppress migration and invasion of cancer cells via the inhibition of epithelial-to-mesenchymal transition (EMT) and EMT-related factors such as TGF-β, ZEB, Slug, and Snail. Besides, NOB inhibits oncogene factors such as STAT3, NF-κB, Akt, PI3K, Wnt, and so on. Noteworthy, onco-suppressor factors such as microRNA-7 and -200b undergo upregulation by NOB in cancer therapy. These onco-suppressor and oncogene pathways and mechanisms are discussed in this review.
