Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

被引:1
作者
Kucukkaraduman, Baris [1 ]
Cicek, Ekin Gokce [1 ]
Akbar, Muhammad Waqas [1 ]
Canli, Secil Demirkol [2 ]
Vural, Burcak [3 ]
Gure, Ali Osmay [4 ]
机构
[1] Bilkent Univ, Dept Mol Biol & Genet, TR-06800 Ankara, Turkey
[2] Hacettepe Univ, Mol Pathol Applicat & Res Ctr, TR-06100 Ankara, Turkey
[3] Istanbul Univ, Aziz Sancar Inst Expt Med, Dept Genet, TR-34093 Istanbul, Turkey
[4] Acibadem Univ, Dept Med Biol, TR-34684 Istanbul, Turkey
关键词
natural products; cancer; chemotherapy resistance; epithelial-to-mesenchymal transition; mesenchymal-to-epithelial transition; CHEMOTHERAPEUTIC DRUGS; LUNG-CANCER; TUMOR-CELLS; RESISTANCE; CURCUMIN; METFORMIN; GROWTH; EMT; 5-FLUOROURACIL; METASTASIS;
D O I
10.3390/molecules26195858
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:15
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