Research Article In Vitro Anticancer Effect of Gedunin on Human Teratocarcinomal (NTERA-2) Cancer Stem-Like Cells Luxmiga Tharmarajah, Sameera Ranganath Samarakoon, Meran Keshawa Ediriweera, Poorna Piyathilaka, Kamani Hemamamla Tennekoon, Kanishka Sithira Senathilake, Umapriyatharshini Rajagopalan, Prasanna Bandula Galhena, and Ira Thabrew Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, 90 Cumaratunga Munidasa Mawatha, 03 Colombo, Sri Lanka Correspondence should be addressed to Sameera Ranganath Samarakoon; sam@ibmbb.cmb.ac.lk Received 5 April 2017; Accepted 9 May 2017; Published 7 June 2017 Academic Editor: Dong-Wook Han Copyright © 2017 Luxmiga Tarmarajah et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Gedunin is one of the major compounds found in the neem tree (Azadirachta indica). In the present study, antiproliferative potential of gedunin was evaluated in human embryonal carcinoma cells (NTERA-2, a cancer stem cell model) and peripheral blood mononuclear cells (PBMCs), using Sulforhodamine (SRB) and WST-1 assays, respectively. Te efects of gedunin on expression of heat shock protein 90 (HSP90), its cochaperone Cdc37, and HSP client proteins (AKT, ErbB2, and HSF1) were evaluated by real- time PCR. Efects of gedunin on apoptosis were evaluated by (a) apoptosis associated morphological changes, (b) caspase 3/7 expression, (c) DNA fragmentation, (d) TUNEL assay, and (e) real-time PCR of apoptosis related genes (Bax, p53, and survivin). Gedunin showed a promising antiproliferative efect in NTERA-2 cells with IC 50 values of 14.59, 8.49, and 6.55 g/mL at 24, 48, and 72 h afer incubations, respectively, while exerting a minimal efect on PBMCs. Expression of HSP90, its client proteins, and survivin was inhibited and Bax and p53 were upregulated by gedunin. Apoptosis related morphological changes, DNA fragmentation, and increased caspase 3/7 activities confrmed the proapoptotic efects of gedunin. Collectively, results indicate that gedunin may be a good drug lead for treatment of chemo and radiotherapy resistant cancer stem cells. 1. Introduction Cancer stem cells (CSCs) are considered as initiators of tumor development and progression [1]. Tey possess stem cell characteristics such as proliferation, self-renewal, and difer- entiation into all cell types of the original tumor [2]. Tese CSCs are resistant to conventional chemotherapy, radiation therapy, and various natural and synthetic anticancer drugs, thus causing relapse of cancer afer conventional treatments [3]. Terefore, it is essential to identify novel drug leads that not only target cancer descendant malignant cells, but also target CSCs without damaging normal cells [4]. As CSCs possess some unique dynamics and features, they can be targeted by several methods, including sensitization to natural or synthetic compounds, induction of diferentiation into other cell types, and restricting self-renewal [5]. Among clinically approved anticancer drugs, approxi- mately 60% are natural products derived from plants and microorganisms [6]. Te hedgehog, Wnt/-catenin, and Notch-mediated signaling pathways are considerd to be important in CSCs diferentiation and self-renewal [7]. Several natural compounds have been reported to target these signaling pathways of CSCs. Cyclopamine, an alkaloid frst isolated from Veratrum californicum, has been reported to target hedgehog signaling pathway [8]. Epigallocatechin gallate (EGCG), one of the main compounds in tea, has been reported to inhibit Wnt/-catenin signaling pathway [9]. It has also been reported that Vitamin D and its analogs could inhibit Notch and Wnt/-catenin signaling pathways [10]. Moreover, curcumin and piperine, well-known anticancer compounds, have also been reported to target breast CSCs [11]. Hindawi BioMed Research International Volume 2017, Article ID 2413197, 9 pages https://doi.org/10.1155/2017/2413197