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

Kucukkaraduman B., Cicek E. G., Akbar M. W., Demirkol Canlı S., Vural B., Güre A. O.

MOLECULES, cilt.26, sa.19, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 26 Sayı: 19
  • Basım Tarihi: 2021
  • Doi Numarası: 10.3390/molecules26195858
  • Dergi Adı: MOLECULES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Metadex, Veterinary Science Database, Directory of Open Access Journals, Civil Engineering Abstracts
  • Anahtar Kelimeler: 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
  • İstanbul Üniversitesi Adresli: Evet

Özet

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.