Cancer Letters 424 (2018) 46e69
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Cancer Letters journal homepage: www.elsevier.com/locate/canlet
Original Articles
Phytochemicals as potent modulators of autophagy for cancer therapy Mohammad Amin Moosavi a, *, Atousa Haghi b, 1, Marveh Rahmati c, 1, Hiroaki Taniguchi d, Andrei Mocan e, Javier Echeverría f, Vijai K. Gupta g, Nikolay T. Tzvetkov h, i, Atanas G. Atanasov d, j, ** a
Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, P.O Box:14965/161, Tehran, Iran Young Researchers & Elite Club, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran c Cancer Biology Research Center, Tehran University of Medical Sciences, Tehran, Iran d Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland e Department of Pharmaceutical Botany, "Iuliu Hat¸ ieganu" University of Medicine and Pharmacy, Gheorghe Marinescu 23 Street, 400337 Cluj-Napoca, Romania f Facultad de Química y Biología, Universidad de Santiago de Chile, Casilla 40, Correo 33, Santiago 9170022, Chile g Department of Chemistry and Biotechnology, ERA Chair of Green Chemistry, Tallinn University of Technology, 12618 Tallinn, Estonia h Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany i NTZ Lab Ltd., Krasno Selo 198, Sofia 1618, Bulgaria j Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria b
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Article history: Received 24 September 2017 Received in revised form 18 February 2018 Accepted 19 February 2018
The dysregulation of autophagy is involved in the pathogenesis of a broad range of diseases, and accordingly universal research efforts have focused on exploring novel compounds with autophagymodulating properties. While a number of synthetic autophagy modulators have been identified as promising cancer therapy candidates, autophagy-modulating phytochemicals have also attracted attention as potential treatments with minimal side effects. In this review, we firstly highlight the importance of autophagy and its relevance in the pathogenesis and treatment of cancer. Subsequently, we present the data on common phytochemicals and their mechanism of action as autophagy modulators. Finally, we discuss the challenges associated with harnessing the autophagic potential of phytochemicals for cancer therapy. © 2018 Elsevier B.V. All rights reserved.
Keywords: Autophagy Cancer Cell death Oxidative stress Phytochemical Therapy
Introduction Phytochemicals (phyton means “plant” in Greek) are naturally occurring plant-based compounds. They are mostly composed of non-nutrient chemicals that are found in grains, vegetables, and fruits [1,2]. While over ten thousand phytochemicals have been identified, many others remain unknown and need to be identified [1e3]. Important groups of phytochemicals include phenolic compounds, alkaloids, terpenes, organosulfides, and
* Corresponding author. National Institute of Genetic Engineering and Biotechnology, P.O Box:14965/161, Tehran, Iran. ** Corresponding author. Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, 05-552 Jastrzebiec, Poland. E-mail addresses:
[email protected] (M.A. Moosavi), atanas.atanasov@ univie.ac.at (A.G. Atanasov). 1 These two authors contributed equally. https://doi.org/10.1016/j.canlet.2018.02.030 0304-3835/© 2018 Elsevier B.V. All rights reserved.
glucosinolates [1,4,5]. The health benefits of phytochemicals are mostly associated with reducing the risk of developing diverse human diseases [3,5,6]. Such plant-based compounds are easily accessible, often with less toxic effects than synthetic molecules, and possess a wide range of biological and pharmacological effects, including anti-microbial, anti-tumoral, anti-mutagenic, and anti-oxidant or pro-oxidant activities [1,3,5e9]. Positive outcomes in clinical trials have led to the introduction of several phytochemicals into clinical practice in recent decades [6,10]. Particularly in cancer and other chronic diseases that are associated with excessive production of reactive oxygen species (ROS), both the anti-oxidant and pro-oxidant properties of phytochemicals can be utilized to prevent or eradicate cancer, respectively [3,9,11e13]. For example, enriched flavonoids from vegetables and fruits show potent ROS modulating and anticancer effects, alone or in combination with standard chemotherapy [14]. Mechanistically, the anti-cancer effects of
