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Chloroquine enhances the chemotherapeutic activity of 5-fluorouracil in a colon cancer cell line via cell cycle alteration

Title
Chloroquine enhances the chemotherapeutic activity of 5-fluorouracil in a colon cancer cell line via cell cycle alteration
Author
최정혜
Keywords
Chloroquine; colon cancer; autophagy; 5-fluorouracil; cell cycle; AUTOPHAGY; P53; EXPRESSION; THERAPY; BIOLOGY; ASSAY
Issue Date
2012-07
Publisher
WILEY
Citation
APMIS, Jul 2012, 120(7), p597-604. 8p.
Abstract
Autophagy is a conserved catabolic process that degrades cytoplasmic proteins and organelles for recycling. The role of autophagy in tumorigenesis is controversial because autophagy can be either protective or damaging to tumor cells, and its effects may change during tumor progression. A number of cancer cell lines have been exposed to chloroquine, an anti-malarial drug, with the aim of inhibiting cell growth and inducing cell death. In addition, chloroquine inhibits a late phase of autophagy. This study was conducted to investigate the anti-cancer effect of autophagy inhibition, using chloroquine together with 5-fluorouracil (5-FU) in a colon cancer cell line. Human colon cancer DLD-1 cells were treated with 5-FU (10 mu) or chloroquine (100 mu), or a combination of both. Autophagy was evaluated by western blot analysis of microtubule-associated protein light chain3 (LC3). Proliferative activity, alterations of the cell cycle, and apoptosis were measured by MTT assays, flow cytometry, and western blotting. LC3-II protein increased after treatment with 5-FU, and chloroquine potentiated the cytotoxicity of 5-FU. MTT assays showed that 5-FU inhibited proliferation of the DLD-1 cells and that chloroquine enhanced this inhibitory effect of 5-FU. The combination of 5-FU and chloroquine induced G1 arrest, up-regulation of p27 and p53, and down-regulation of CDK2 and cyclin D1. These results suggest that chloroquine may potentiate the anti-cancer effect of 5-FU via cell cycle inhibition. Chloroquine potentiates the anti-cancer effect of 5-FU in colon cancer cells. Supplementation of conventional chemotherapy with chloroquine may provide a new cancer therapy modality.
URI
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1600-0463.2012.02876.xhttp://repository.hanyang.ac.kr/handle/20.500.11754/69379
ISSN
0903-4641
DOI
10.1111/j.1600-0463.2012.02876.x
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COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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