Recent Patents on Anti-Cancer Drug Discovery Send Orders for Reprints to reprints@benthamscience.ae 224 Recent Patents on Anti-Cancer Drug Discovery, 2018, 13, 224-239 REVIEW ARTICLE Anti-Oxidants as Chemopreventive Agents in Prostate Cancer: A Gap Between Preclinical and Clinical Studies Monireh Mohsenzadegan 1,* , Farhad Seif 2 , Mohammad M. Farajollahi 3 and Majid Khoshmirsafa 2 1 Department of Medical Laboratory Science, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran; 2 Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; 3 Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran A R T I C L E H I S T O R Y Received: November 13, 2017 Revised: February 08, 2018 Accepted: February 11, 2018 DOI: 10.2174/1574892813666180213164700 Abstract: Background: Tumor cells may be expressed as a result of oxidative stress. The extent of oxidative stress correlates with the aggressive and metastatic potency of cancer. Objective: One simple way to control prostate cancer is through chemoprevention which refers to the administration of natural or synthetic agents to block, reverse, or delay the process of carcinogenesis. The most chemopreventive agents are antioxidants in nature. Methods: In this review, we summarized the effects of dietary antioxidants with a focus on their mo- lecular mechanisms and possible roles in the treatment of prostate cancer cells. We also reported the recent outcomes of laboratory and/or clinical trials of antioxidants in prostate cancer patients. Results: Numerous pre-clinical studies showed that antioxidants protect DNA against being damaged by Reactive Oxygen Species (ROS), thereby genetic mutations causing cancer are likely to be prevented. However, the clinical trial results showed that antioxidants have yielded mixed outcomes or benefitted only a subgroup of the population. Conclusion: A greater understanding of the molecular events associated with antioxidants will enhance the development of treatment and could result in better strategies for the chemoprevention of prostate cancer. Recent patents also suggest that anti-oxidant compounds can be effective for the prevention and the treatment of prostate cancer. Keywords: Antioxidants, chemopreventive agents, preclinical study, prostate cancer, reactive oxygen species, recent patents, clinical study. 1. INTRODUCTION Prostate Cancer (PCa) is one of the most common cancers in the male population. It is a disease with various symptoms ranging from asymptomatic to an aggressive systemic malig- nancy [1]. Current treatments for localized PCa include sur- gery, radiotherapy, and active monitoring. The current ap- proaches chosen for advanced and metastatic cancer thera- pies are hormone therapy and chemotherapy [2]. However, these therapies are currently unable to completely eliminate androgen-resistant PCa cells that remain after hormone ther- apy in the form of metastatic PCa. In fact, progression and metastasis of androgen-independent PCa are major causes of death due to PCa [3, 4]. The epidemiologic results suggest that in addition to sex hormones and genetic susceptibility, *Address correspondence to this author at the Department of Medical Labo- ratory Science, Faculty of Allied Medical Sciences, Iran University of Medi- cal Sciences (IUMS), Hemmat Highway, Tehran, Iran; Tel: +982186704681; Fax: +982188622533; E-mails: monirehmohsenzadegan@gmail.com, mohsenzadegan.m@iums.ac.ir environmental exposures such as diet, in particular, dietary fat and low antioxidant compounds play important roles in prostate carcinogenesis [5]. Nutritional factors such as meat, fat and dairy, which are commonly consumed in western societies have associated with a greater risk of cancer [6]. Therefore, novel approaches seem essential for the treatment of PCa. Antioxidants are one of the major candidates for chemoprevention of PCa. Chemoprevention is known for the use of natural or synthetic agents to inhibit, reverse or pre- vent the cancer progression [7]. The potential mechanism of antioxidant effectiveness is catalyzing and transforming ROS-mainly superoxide-which may play a pivotal role in PCa pathogenesis. In the past studies, there were contradic- tory reports discussing antioxidant effects on progression or regression of PCa. There were limitations in previous review studies; Thapa et al. have mentioned some antioxidants as chemopreventive agents in PCa in 2012, however, did not review with scrutiny antioxidant effects on PCa cells [7]. Vance et al. also reviewed a very limited number of antioxi- dants in PCa including vitamins and green tea until 2013 [8]. 2212-3970/18 $100.00+.00 © 2018 Bentham Science Publishers