In Vitro Anticancer Effect of Gedunin on Human Teratocarcinomal (NTERA-2) Cancer Stem-Like Cells

作者：Tharmarajah Luxmiga; Samarakoon Sameera Ranganath; Ediriweera Meran Keshawa; Piyathilaka Poorna; Tennekoon Kamani Hemamamla; Senathilake Kanishka Sithira; Rajagopalan Umapriyatharshini; Galhena Prasanna Bandula; Thabrew Ira

来源：Biomed Research International, 2017, 2017: 2413197.

DOI：10.1155/2017/2413197

<jats:p>Gedunin is one of the major compounds found in the neem tree<jats:italic> (Azadirachta indica)</jats:italic>. 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. The effects 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. Effects 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 (<jats:italic>Bax</jats:italic>,<jats:italic> p53, </jats:italic>and<jats:italic> survivin</jats:italic>). Gedunin showed a promising antiproliferative effect in NTERA-2 cells with IC<jats:sub>50</jats:sub> values of 14.59, 8.49, and 6.55 <jats:italic>μ</jats:italic>g/mL at 24, 48, and 72 h after incubations, respectively, while exerting a minimal effect on PBMCs. Expression of HSP90, its client proteins, and<jats:italic> survivin</jats:italic> was inhibited and<jats:italic> Bax</jats:italic> and<jats:italic> p53</jats:italic> were upregulated by gedunin. Apoptosis related morphological changes, DNA fragmentation, and increased caspase 3/7 activities confirmed the proapoptotic effects of gedunin. Collectively, results indicate that gedunin may be a good drug lead for treatment of chemo and radiotherapy resistant cancer stem cells.</jats:p>

• 出版日期2017