Your browser doesn't support javascript.
loading
Demethoxycurcumin sensitizes the response of non-small cell lung cancer to cisplatin through downregulation of TP and ERCC1-related pathways.
Lin, Chen-Yuan; Hung, Chin-Chuan; Wang, Charles C N; Lin, Hui-Yi; Huang, Shih-Huan; Sheu, Ming-Jyh.
Afiliación
  • Lin CY; Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taiwan.
  • Hung CC; School of Pharmacy, China Medical University, Taichung 40402, Taiwan.
  • Wang CCN; Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan.
  • Lin HY; School of Pharmacy, China Medical University, Taichung 40402, Taiwan.
  • Huang SH; School of Pharmacy, China Medical University, Taichung 40402, Taiwan.
  • Sheu MJ; School of Pharmacy, China Medical University, Taichung 40402, Taiwan. Electronic address: hsumj@mail.cmu.edu.tw.
Phytomedicine ; 53: 28-36, 2019 Feb.
Article en En | MEDLINE | ID: mdl-30668408
BACKGROUND: Excision repair cross-complementary 1 (ERCC1) overexpression in lung cancer cells is strongly correlated with its resistance to platinum-based chemotherapy. Overexpression of thymidine phosphorylase (TP) reverts platinum-induced cancer cell death. PURPOSE: Curcumin has been reported to enhance antitumor properties through the suppression of TP and ERCC1 in non-small cell lung carcinoma cells (NSCLC). Nevertheless, whether two other curcuminoids, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) from Curcuma longa demonstrate antitumor activity like that of curcumin remain unknown. METHODS: MTT assay was conducted to determine the cell cytotoxicity. Western blotting was used to determine the protein expressions. Docking is the virtual screening of a database of compounds and predicting the strongest binders based on various scoring functions. BIOVIA Discovery Studio 4.5 (D.S. 4.5) were used for docking. RESULTS: Firstly, when compared with curcumin and BDMC, DMC exhibited the most potent cytotoxic effect on NSCLC, most importantly, MRC-5, a lung fetal fibroblast, was insensitive to DMC (under 30 µM). Secondly, DMC alone significantly inhibited on-target cisplatin (CDDP) resistance protein, ERCC1, via PI3K-Akt-snail pathways, and TP protein expression in A549 cells. Thirdly, DMC treatment markedly increased post-target CDDP resistance pathway including Bax and cytochrome c. DMC significantly decreased Bcl-2 protein expressions. Finally, MTT assay indicated that DMC significantly increased CDDP-induced cytotoxicity and was confirmed with an increased Bax/Bcl-2 ratio, indicating upregulation of caspase-3. CONCLUSIONS: We concluded that enhancement of the cytotoxicity to CDDP by coadminstration with DMC was mediated by down-regulation of the expression of TP and ERCC1, regulated by PI3K-Akt-Snail pathway inactivation.
Asunto(s)
Palabras clave

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Carcinoma de Pulmón de Células no Pequeñas / Curcumina / Proteínas de Unión al ADN / Endonucleasas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Idioma: En Revista: Phytomedicine Año: 2019 Tipo del documento: Article País de afiliación: Taiwán

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Carcinoma de Pulmón de Células no Pequeñas / Curcumina / Proteínas de Unión al ADN / Endonucleasas / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Idioma: En Revista: Phytomedicine Año: 2019 Tipo del documento: Article País de afiliación: Taiwán