The anti-proliferative and anti-androgenic activity of different pomegranate accessions Ola Orgil a,b , Limor Spector a , Doron Holland c , Jamal Mahajna a,b , Rachel Amir a,b, * a Migal Galilee Technology Center, P.O. Box 831, Kiryat Shmona 11016, Israel b Tel Hai College, Upper Galilee, Israel c Institute of Plant Sciences,Agricultural Research Organization, Newe Ya’ar Research Center, Ramat Yishay 30095, Israel ARTICLE INFO Article history: Received 6 June 2016 Received in revised form 24 July 2016 Accepted 15 August 2016 Available online ABSTRACT This study monitored the anti-proliferative activity of pomegranate (Punica granatum L.) peel homogenates against breast (MCF7 and MDA-MB-453) and prostate (LNCaP and PC-3) cancer cell lines using 29 different accessions to study the natural diversity in these accessions. Using MTT method, it was revealed that high anti-proliferative activity was observed against MCF7, MDA-MB-453 and LNCaP (androgen-dependent) cell lines for most accessions, while the androgen-independent prostate cancer cell line, PC-3, exhibited relatively high resis- tance. Peel extracts displayed the highest LNCaP inhibition activity compared to aril juice and seed homogenates. Eight accessions exhibiting the highest anti-proliferative activity were studied further using the LNCaP and PC-3 cancer cells. IC50 and clonogenicity inhibi- tion were determined. Several accessions were found to inhibit androgen receptor activity but not NF-κB transcription function. This study illustrated the importance of exploiting natural pomegranate variation to identify accessions exhibiting potential selective activity for the treatment of specific types of cancer. © 2016 Elsevier Ltd. All rights reserved. Keywords: Androgen receptor Anti-proliferative activity Cancer cell lines Different accessions Phenolic compounds Pomegranate 1. Introduction Studies have shown that juice from pomegranate (Punica gra- natum L.) (PJ) has high benefit to human health. The juice has high polyphenol and total phenols content (TPC) (Seeram, Zhang, Reed, Krueger, & Vaya, 2006), which act as scavengers of free radicals and reactive oxygen species (ROS) (Aviram et al., 2008). Phenols antioxidative activities have been associated with the reduction of stress-related chronic diseases and age-related dis- orders, such as cardiovascular diseases (Aviram et al., 2008), neurodegeneration and skin deterioration (Quideau, Deffieux, Douat-Casassus, & Pouysegu, 2011). Studies have also shown that PJ exhibits anti-carcinogenic and anti-proliferative activities (Adhami, Khan, & Mukhtar, 2009; Orgil et al., 2014), as well as other health-promoting abilities (Ismail, Sestili, & Akhtar, 2012). Detailed studies have revealed that most of the phenols and polyphenols in PJ are derived from the non-edible sections of * Corresponding author. Laboratory of Plant Science, Migal GalileeTechnology Center, P.O. Box 831, Kiryat Shmona 11016, Israel. Fax: +972 4 6944980. E-mail address: Rachel@migal.org.il (R. Amir). Abbreviations: AR, androgen receptor; ETs, ellagitannins; PJ, pomegranate juice; TPC, total phenols content http://dx.doi.org/10.1016/j.jff.2016.08.024 1756-4646/© 2016 Elsevier Ltd. All rights reserved. Journal of Functional Foods 26 (2016) 517–528 Available online at www.sciencedirect.com journal homepage: www.elsevier.com/locate/jff ScienceDirect