title: Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells.
abstract: 5-Fluorouracil (5-FU) is the most used chemotherapeutic agent in colorectal cancer. However, resistance to this drug is relatively frequent, and new strategies to overcome it are urgently needed. The aim of this work was to determine the antitumor properties of a supercritical fluid rosemary extract (SFRE), alone and in combination with 5-FU, as a potential adjuvant therapy useful for colon cancer patients. This extract has been recognized as a healthy component by the European Food Safety Authority (EFSA). The effects of SFRE both alone and in combination with 5-FU were evaluated in different human colon cancer cells in terms of cell viability, cytotoxicity, and cell transformation. Additionally, colon cancer cells resistant to 5-FU were used to assay the effects of SFRE on drug resistance. Finally, qRT-PCR was performed to ascertain the mechanism by which SFRE potentiates the effect of 5-FU. Our results show that SFRE displays dose-dependent antitumor activities and exerts a synergistic effect in combination with 5-FU on colon cancer cells. Furthermore, SFRE sensitizes 5-FU-resistant cells to the therapeutic activity of this drug, constituting a beneficial agent against both 5-FU sensitive and resistant tumor cells. Gene expression analysis indicates that the enhancement of the effect of 5-FU by SFRE might be explained by the downregulation of TYMS and TK1, enzymes related to 5-FU resistance.
authors.affiliation: IMDEA-Food Institute, CEI UAM+CSIC, C/Faraday 7, 28049 Madrid, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: González-Vallinas
authors.forename: Susana
authors.initials: S
authors.lastname: Molina
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Vicente
authors.forename: Ana
authors.initials: A
authors.lastname: de la Cueva
authors.forename: Teodoro
authors.initials: T
authors.lastname: Vargas
authors.forename: Susana
authors.initials: S
authors.lastname: Santoyo
authors.forename: Mónica R
authors.initials: MR
authors.lastname: García-Risco
authors.forename: Tiziana
authors.initials: T
authors.lastname: Fornari
authors.forename: Guillermo
authors.initials: G
authors.lastname: Reglero
authors.forename: Ana
authors.initials: A
authors.lastname: Ramírez de Molina
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology; D027542:Rosmarinus / Q000737:chemistry*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D005472:Fluorouracil