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Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines
Authors:Baris Kucukkaraduman  Ekin Gokce Cicek  Muhammad Waqas Akbar  Secil Demirkol Canli  Burcak Vural  Ali Osmay Gure
Affiliation:1.Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey; (B.K.); (E.G.C.); (M.W.A.);2.Molecular Pathology Application and Research Center, Hacettepe University, Ankara 06100, Turkey;3.Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul 34093, Turkey;4.Department of Medical Biology, Acibadem University, Istanbul 34684, Turkey
Abstract:
Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.
Keywords:natural products   cancer   chemotherapy resistance   epithelial-to-mesenchymal transition   mesenchymal-to-epithelial transition
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