Research Article Open Access Volume 2 • Issue 2 • 1000117 Chemotherapy ISSN: 2167-7700 CMT, an open access journal Open Access Research Article Chemotherapy: Open Access Uddin et al., Chemotherapy 2013, 2:2 http://dx.doi.org/10.4172/2167-7700.1000117 *Corresponding author: Ghias Uddin, Institute of Chemical Sciences, University of Peshawar, Peshawar-25120, Pakistan, E-mail: drghiasuddin@hotmail.com, Ghiasuddin@upesh.edu.pk Received July 31, 2013; Accepted August 17, 2013; Published August 26, 2013 Citation: Uddin G, Rauf A, Siddiqui BS, Khan A, Marasini BP, et al. (2013) Broad Spectrum Anticancer Activity of Pistagremic Acid. Chemotherapy 2: 117. doi:10.4172/2167-7700.1000117 Copyright: © 2013 Uddin G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Keywords: Pistacia integerrima; Pistagremic acid; Antiproliferative agent; Anticancer agent Introduction Pistacia integerrima belongs to family Anacardiacea and found in eastern Himalayan range [1]. he leaves, bark and galls of the plant are generally used for the treatment of cough, asthma, fever, vomiting, diarrhea, infection, hyperuricemia, hepatitis and other liver disorders [2-7]. Cancer is one of the notorious and lethal diseases responsible for 7.6 million deaths (approx. 13% of all deaths) with 12.7 million new cases in 2008, that are projected to continue rising, with an estimated 13.1 million deaths with are 22.2 million cases in 2030 [8,9]. Although various types of cancer reported, cancers of the prostate, lung, and liver the most commonly reported worldwide. here is similar index as the worldwide to developing countries like Pakistan [9]. Researchers have been spending several decades to identify efective agents against cancer which is one of the leading causes of death worldwide. hus, about 60% of anticancer drugs are structural modiication and their analogues from the natural sources such as vinblastine, taxol and camptothecin [10]. However, the management of cancer is still not up to mark and always needs to ind out new chemotherapeutic agents. In continuation of our previous investigation on the bioactivities of pistagremic acid (Figure 1) [11], which was evaluated for its cytotoxic efects against NCI 60-cell panel on eight organs (leukemia, non-small cell lung cancer, colon, CNS, melanoma, ovarian, prostate, renal and breast) at National Cancer Institute (NCI) USA, showed signiicant inhibition of human cancer cell lines. Materials and Methods Pistacia integerrima galls were collected from Razagram, Khyber Pakhtunkhwa, Pakistan in February, 2010 and identiied as P. integerrima by Prof. Dr. Abdur Rashid, Department of Botany, University of Peshawar. A voucher specimen (RF-895) preserved in the herbarium of the Department of Botany, University of Peshawar, Pakistan. he plant material was shade-dried at room temperature, grinded into powder and subsequently successively extracted repeatedly (thrice) with methanol (MeOH). he combined methanolic extracts were freed of the solvent under vacuum to obtained thick syrup. hen 400 g of the concentrated methanolic extract was successively partitioned between n-hexane/water, chloroform/water, ethyl acetate/ water and butanol/water. he chloroform fraction was concentrated under vacuum pressure and 10 g of it was subjected to silica gel column chromatography, eluting with n-hexane, n-hexane-ethyl acetate (EtOAc) in an increasing order of polarity. As a result, 13 fractions (RF-1 to RF-13) were obtained based on TLC proiles. Fraction RF-4 (90 mg, eluted n-hexane-EtOAc, 82:18) aforded colorless crystals of various sizes which were separated from the solution by decantation. he crystals were re-crystallized with appropriate solvents (n-hexane- acetone, 4:1). he chemical structure of the pure crystalline compound was identiied as 2-Methyl-6-(4, 4, 10, 13, 14-pentamethyl-3-xo-2, 3, 4, 5, 6, 7, 10, 11, 12, 13, 14, 15, 16, 17-tetradecahydro-1H-cyclopenta [a] phenanthren-17-yl) hept-2-enoic acid (pistagremic acid) by X-ray crystallography analysis as reported earlier [12]. Anticancer Assay he anticancer assay against cancer cell lines were conducted at NCI by using Sulphorhodamine B assay [13,14]. hese cancer cell lines were grown in RPMI-1640 medium, supplemented with fetal bovine serum (10%) and L-glutamine (2 mM). he culture lasks were kept in CO 2 Broad Spectrum Anticancer Activity of Pistagremic Acid Ghias Uddin 1 *, Abdur Rauf 1 , Bina Shaheen Siddiqui 2 , Ajmal Khan 2 , Bishnu P Marasini 2 , Abdul Latif 1 and Thomas J Simpson 3 1 Institute of Chemical Sciences, University of Peshawar, Peshawar-25120, Pakistan 2 H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan 3 School of Chemistry, University of Bristol, Bristol BS8 1TS, UK Abstract Background: Pistagremic acid; 3-methyl-7-(4,4,10,13,14-pentamethyl-3-2,3,4,5,6,7,10,11,12,13,14,15,16,17- tetradecahydro-1H-cyclopenta[a]phenanthr-en-17-yl)-oct-3-enoic acid was isolated from the chloroform fraction of Pistacia integerrima. Cytotoxic evaluation against NCI-60 DTP human tumor cell line was performed. Methods: The anticancer assays for this compound were performed in accordance with the protocol of the Drug Evaluation Branch, of the National Cancer Institute (NCI) Developmental Therapeutic Program (www.dtp.nci.nih.gov) for their anticancer activity in vitro. Results: It showed broad spectrum antiproliferative activity with an average GI 50 , and TGI, values 0.103 µM and 0.259 µM, respectively. It also showed signiicant LC 50 value at the average 0.634 µM against all cell lines excluding K-562, RPMI-8226, NCI-H226, and NCI-H460 cell-lines. Conclusions: Pistagremic acid showed cytotoxicity for all tested cancer cell line, thus it may serve as a potential structure lead for the development of new anticancer drugs.