Licorice (Glycyrrhiza glabra L.)-Derived Phytochemicals Target Multiple Signaling Pathways to Confer Oncopreventive and Oncotherapeutic Effects

Abstract

Hardeep Singh Tuli,1 Vivek Kumar Garg,2 Jinit K Mehta,3 Ginpreet Kaur,3 Ranjan K Mohapatra,4 Kuldeep Dhama,5 Katrin Sak,6 Ajay Kumar,7 Mehmet Varol,8 Diwakar Aggarwal,1 Uttpal Anand,9 Jagjit Kaur,10 Ross Gillan,11 Gautam Sethi,12 Anupam Bishayee11 1Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, India; 2Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, Punjab, India; 3Department of Pharmacology, Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, Shri Vile Parle Kelavani Mandal, Narsee Monjee Institute of Management Studies, Mumbai, Maharashtra, India; 4Department of Chemistry, Government College of Engineering, Keonjhar, Odisha, India; 5Division of Pathology, Indian Council of Agricultural Research-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India; 6NGO Praeventio, Tartu, Estonia; 7Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, Punjab, India; 8Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey; 9Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; 10Centre of Excellence in Nanoscale Biophotonics, Graduate School of Biomedical Engineering, Faculty of Engineering, The University of New South Wales, Sydney, Australia; 11College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL, USA; 12Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCorrespondence: Anupam Bishayee; Hardeep Singh Tuli, Email [email protected]; [email protected]; [email protected]: Cancer is a highly lethal disease, and its incidence has rapidly increased worldwide over the past few decades. Although chemotherapeutics and surgery are widely used in clinical settings, they are often insufficient to provide the cure for cancer patients. Hence, more effective treatment options are highly needed. Although licorice has been used as a medicinal herb since ancient times, the knowledge about molecular mechanisms behind its diverse bioactivities is still rather new. In this review article, different anticancer properties (antiproliferative, antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory effects) of various bioactive constituents of licorice (Glycyrrhiza glabra L.) are thoroughly described. Multiple licorice constituents have been shown to bind to and inhibit the activities of various cellular targets, including B-cell lymphoma 2, cyclin-dependent kinase 2, phosphatidylinositol 3-kinase, c-Jun N-terminal kinases, mammalian target of rapamycin, nuclear factor-κB, signal transducer and activator of transcription 3, vascular endothelial growth factor, and matrix metalloproteinase-3, resulting in reduced carcinogenesis in several in vitro and in vivo models with no evident toxicity. Emerging evidence is bringing forth licorice as an anticancer agent as well as bottlenecks in its potential clinical application. It is expected that overcoming toxicity-related obstacles by using novel nanotechnological methods might importantly facilitate the use of anticancer properties of licorice-derived phytochemicals in the future. Therefore, anticancer studies with licorice components must be continued. Overall, licorice could be a natural alternative to the present medication for eradicating new emergent illnesses while having just minor side effects.Keywords: licorice, cancer, apoptosis, cell cycle, angiogenesis, treatment, nano-delivery

Keywords

• licorice
• cancer
• apoptosis
• cell cycle
• angiogenesis
• treatment
• nano-delivery