Original article Isolation of a new resorcinolic lipid from Mangifera zeylanica Hook.f. bark and its cytotoxic and apoptotic potential Meran Keshawa Ediriweera a , Kamani Hemamala Tennekoon a, *, Sameera Ranganath Samarakoon a , Achyut Adhikari b, *, Ira Thabrew a , E. Dilip de Silva a a Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, 90, Cumaratunga Munidasa Mawatha, Colombo 03, Sri Lanka b HEJ Research Institute of Chemistry, University of Karachi, Pakistan A R T I C L E I N F O Article history: Received 4 November 2016 Received in revised form 19 January 2017 Accepted 19 January 2017 Keywords: Resorcinolic lipid Mangifera zeylanica Cytotoxicity Apoptosis Anti cancer activity Oxidative stress A B S T R A C T Mangifera zeylanica is a plant endemic to Sri Lanka and its bark has been used in traditional medicine to treat some cancers. This study was aimed to isolate potentially cytotoxic compound/s from the hexane extract of the bark of M. zeylanica by bio-activity guided fractionation. The structure of the isolated compound (1) was elucidated using 1 H, 13 C NMR and mass spectrometric techniques. Compound 1 was identified as a new resorcinolic lipid (5-((8Z, 11Z, 14Z)-hexatriaconta-8, 11, 14-trienyl) benzene-1,3-diol). Apoptotic potential of the isolated compound was determined only in MCF-7 (estrogen receptor positive) breast cancer cells to which it was more cytotoxic than to normal mammary epithelial cells. Oxidative stress markers [reactive oxygen species (ROS), glutathione levels (GSH) and glutathione-S-transferase (GSH)] were also determined in MCF-7 cells treated with compound 1. Treatment with compound 1 led to an increase in caspase 7 activity, morphological features of apoptosis and DNA fragmentation in MCF-7 cells. Furthermore, it also led to an increase in ROS and GST levels while depleting GSH levels. Results of this study suggest that isolated new resorcinolic lipid can induce apoptosis in MCF-7 cells, possibly via oxidative stress mechanism. © 2017 Elsevier Masson SAS. All rights reserved. 1. Introduction Despite the availability of modern cancer therapeutics and diagnostic methods, breast cancer is the most common form of cancer and a leading cause of cancer related mortality in women worldwide [1]. As in most other countries, breast cancer is the leading cancer among Sri Lankan women [2]. Age, family history, marital status, early menarche, use of oral contraceptives and late menopause are some of the risk factors for breast cancer [3]. However, pathophysiology of breast cancer is highly complex and partially understood. Even though, the available treatment options are effective in early stage of breast cancer, their use is limited in the treatment of late stage breast cancer [4]. Chemotherapy, surgery, radiotherapy and hormonal therapy are currently used in the treatment of breast cancer [5]. Among these, chemotherapy and radiotherapy cause severe side effects to the patient [6]. Another cancer affecting women with a high mortality rate is ovarian cancer. It is the fourth leading cancer among Sri Lankan women whereas it ranks as the eighth most common gynecological malignancy worldwide. Ovarian cancer is usually treated with surgery, chemotherapy and radiotherapy [1,2]. Natural products play an important role in the development of new anti-cancer drugs and a considerable number of established cancer drugs are derived from natural sources [7]. Natural compounds such as curcumin, sulfarophane and resveratrol are currently receiving greater attention among researchers as potential adjuvant anti-cancer drugs with fewer side effects [8]. Resorcinolic lipids are secondary metabolites bio-synthesized by plants, animals, fungi and bacteria [9]. These compounds contain a phenolic head group and an alkyl side chain/s [10]. Several groups have previously reported the cytotoxic and apoptotic potential of a number of resorcinolic lipids in different cancer cell lines [hepatoma cells (HepG2), melanoma cells (B-16), lymphoma cells (L5178Y and P388D1), embryonic carcinoma cells (PC-13) and breast cancer cells (MCF-7 and MDA-MB-231)] [9–11]. Mangifera zeylanica (family, Anacardiaceae) is a plant endemic to Sri Lanka [12]. It is commonly known as ‘Etamba’ and bears edible fruits. Its bark has been traditionally used to treat diseases * Corresponding authors. E-mail addresses: mk.ediriweera@gmail.com (M.K. Ediriweera), kamani@ibmbb.cmb.ac.lk (K.H. Tennekoon), sam@ibmbb.cmb.ac.lk (S.R. Samarakoon), adhikarimine@yahoo.com (A. Adhikari), irathab@gmail.com (I. Thabrew), edilip.desilva@gmail.com (E. Dilip de Silva). http://dx.doi.org/10.1016/j.biopha.2017.01.176 0753-3322/© 2017 Elsevier Masson SAS. All rights reserved. Biomedicine & Pharmacotherapy 89 (2017) 194–200 Available online at ScienceDirect www.sciencedirect.com