Research review paper Plant-derived epigenetic modulators for cancer treatment and prevention Michael Schnekenburger a , Mario Dicato a , Marc Diederich b, ⁎ a Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg b Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea abstract article info Available online xxxx Keywords: Epigenetics Natural compounds Cell death Proliferation Clinical trials Cancer therapy Cancer prevention Carcinogenesis is a complex and multistep process that involves the accumulation of successive transformational events driven by genetic mutations and epigenetic alterations that affect major cellular processes and pathways such as proliferation, differentiation, invasion and survival. Massive deregulation of all components of the epige- netic machinery is a hallmark of cancer. These alterations affect normal gene regulation and impede normal cel- lular processes including cell cycle, DNA repair, cell growth, differentiation and apoptosis. Since epigenetic alterations appear early in cancer development and represent potentially initiating events during carcinogenesis, they are considered as promising targets for anti-cancer interventions by chemopreventive and chemotherapeu- tic strategies using epigenetically active agents. In this field, plant-derived compounds have shown promise. Here, we will give an overview of plant-derived compounds displaying anticancer properties that interfere with the epigenetic machinery. © 2014 Elsevier Inc. All rights reserved. Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Plant-derived epigenetic modulators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3,3′-Diindolylmethane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Butyrate and its derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Curcumin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 (-)-Epigallocatechin-3-gallate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Genistein and daidzein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Nordihydroguaiaretic acid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Quercetin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Resveratrol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Sulforaphane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Critical assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Conclusions and further directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Introduction The field of epigenetics investigates heritable changes in phenotype (i.e. gene expression) without a change in the primary DNA sequence. Epigenetic mechanisms namely DNA methylation, histone modifications, and regulatory RNA-mediated gene silencing (non-cod- ing RNA) synergize to sculpt chromatin structure and tune gene expres- sion and therefore are essential for normal development and differentiation of cells. Consequently, epigenetic alterations are associ- ated to the onset and development of cancer (Florean et al., 2011; Karius et al., 2012; Schnekenburger and Diederich, 2011, 2012). In human, DNA methylation corresponds to the addition of a methyl group to cytosine within CpG dinucleotides to form 5-methylcytosine. Biotechnology Advances xxx (2014) xxx–xxx ⁎ Corresponding author. Tel.: +82 2 880 8919. E-mail address: marcdiederich@snu.ac.kr (M. Diederich). JBA-06801; No of Pages 10 http://dx.doi.org/10.1016/j.biotechadv.2014.03.009 0734-9750/© 2014 Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Biotechnology Advances journal homepage: www.elsevier.com/locate/biotechadv Please cite this article as: Schnekenburger M, et al, Plant-derived epigenetic modulators for cancer treatment and prevention, Biotechnol Adv (2014), http://dx.doi.org/10.1016/j.biotechadv.2014.03.009