REVIEW Phytotherapeutics in cancer invasion and metastasis Bahare Salehi 1 | Paolo Zucca 2 | Mehdi Sharifi‐Rad 3 | Raffaele Pezzani 4,5 | Sadegh Rajabi 6 | William N. Setzer 7 | Elena Maria Varoni 8 | Marcello Iriti 9 | Farzad Kobarfard 10,11 | Javad Sharifi‐Rad 10,12 1 Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2 Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy 3 Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol 61663‐335, Iran 4 OU Endocrinology, Dept. Medicine (DIMED), University of Padova, via Ospedale 105, Padova 35128, Italy 5 AIROB, Associazione Italiana per la Ricerca Oncologica di Base, Padova, Italy 6 Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 7 Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA 8 Department of Biomedical, Surgical and Dental Sciences, Milan State University, Milan, Italy 9 Department of Agricultural and Environmental Sciences, Milan State University, Milan, Italy 10 Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 11 Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran 12 Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB, Canada Correspondence Mehdi Sharifi‐Rad, Department of Medical Parasitology, Zabol University Of Medical Sciences, Zabol 61663‐335, Iran. Email: mehdi_sharifirad@gmail.com Raffaele Pezzani, OU Endocrinology, Dept. Medicine (DIMED), University of Padova, via Ospedale 105, Padova 35128, Italy. Email: raffaele.pezzani@unipd.it Marcello Iriti, Department of Agricultural and Environmental Sciences, Milan State University, Milan, Italy. Email: marcello.iriti@unimi.it Javad Sharifi‐Rad, Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Email: javad.sharifirad@gmail.com Cancer is a multifactorial disease, and therefore, a multitarget approach is needed to face the complex cancer biology, based on the combined use of different natural and synthetic anticancer agents able to target synergistically multiple signaling pathways involved in carcinogenesis, including angiogenesis and metastasis. In this view, the plant kingdom represents an unlimited source of phytotherapeutics with promising perspectives in the field of anticancer drug discovery. This narrative review aims to provide an updated overview on the bioactive phytochemicals exhibiting a promising potential as adjuvants in conventional anticancer therapies, with emphasis on antiangiogenic and antimetastatic activities. KEYWORDS adjuvant therapy, anticancer drugs, cancer chemoprevention, chemotherapy, phytochemicals, plant products 1 | INTRODUCTION Carcinogenesis or tumorigenesis is the process through which normal cells are transformed into cancer cells. Main features of the process include cellular, genetic, and epigenetic alterations, which together can form a malignant mass. Cancer cells are abnormal cells, character- ized by uncontrolled growth and potential to escape the normal rules of cell division. Normal cells have signaling pathways that strictly control the cell division, differentiation, and other processes. Autonomous cell division, in cancer cells disregarding these signals, results in uncon- trolled growth and proliferation. Continuous cell proliferation may result in tumor spreading, known as metastasis (Hejmadi, 2009; Mishra et al., 2018). Carcinogenesis, commonly, results from mutagenesis, in turn depending on DNA mutation. This process arises from a continu- ous exposure to carcinogens, which usually include three classes of agents: chemical agents (which commonly induce single nucleotide changes called point mutations), ionizing radiations such as X‐rays (which cause chromosomal breakages and translocations), and viruses (which introduce a short sequence into the host genome). Therefore, in many cases, carcinogenesis depends on the interaction between genes and environmental factors (Alberts et al., 1997; Lodish, 2008) and schematically consists of three phases: initiation, promotion, and Received: 18 October 2017 Revised: 11 March 2018 Accepted: 13 March 2018 DOI: 10.1002/ptr.6087 Phytotherapy Research. 2018;1–25. Copyright © 2018 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/ptr 1