Abstract
Ascertaining the potentials of diet-derived phenolics in eradicating cancer stem cells (CSCs), that proliferate and self-renew extensively leading to the initiation and progression of tumor, may escort significant clinical implications. Recently, we have shown that black raspberry extract (RSE) potentiates pancreatic cancer (PC) cell killing by targeting transcriptional machinery. Herein, we investigated ex vivo the effect of RSE on the regulation of EMT, pluripotency maintaining and other stem cell related molecules in PC-CSCs. CD133+CD44+CD24+ESA+ PC-CSCs isolated from human PC xenografts developed in athymic NCr-nu/nu nude mice with human MiaPaCa2, BXPC3, Panc-1 or Panc-3.27 cells were maintained in vitro. PC-CSCs exposed to RSE (2.0μg) for 3h were assessed for transcriptional regulation of 93 stem cell related molecules using QPCR profiling. Expression and cellular localization of epithelial-to-mesenchymal transition (EMT) markers and pluripotent maintaining factors including ABCG2, E-Cadherin, N-Cadherin, MYB, MYC, Nanog and SOX2 in MiaPaCa2, BXPC3 xenografts were assessed using immunohistochemistry (IHC). The results revealed that RSE significantly inhibited 83, 50 and 54 stem cell related molecules in PC-CSCs isolated from xenografts developed using MiaPaCa2, Panc-1 and Panc 3.27 respectively. Of these, 27 genes were commonly suppressed by RSE in all three PC-CSCs population. Further, IHC staining showed complete repression of EMT and pluripotent markers in both MiaPaCa2 and BXPC3 xenografts. Together, these data imply that RSE may exert selective inhibition of EMT and pancreatic CSCs’ self renewal capacity and, may thus serve as a potential “deliverable” to negate PC initiation and progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1615. doi:1538-7445.AM2012-1615
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