BACKGROUND: The mechanisms that could explain the poor sensitivity to 5-FU in certain colorectal cancer (CRC) cells were investigated and whether or not cotreatment with low doses of selenium would offer a therapeutic benefit was explored. MATERIALS AND METHODS: Four CRC cell lines (Caco2, RKO, DLD1 and HT-29) with defined tumor signatures and seven different chemical forms of selenium were tested. RESULTS: 5-FU partially inhibited the HT-29 and RKO cells, but had a weak effect on the DLD1 and almost none on the Caco2 cells. Selenous acid and sodium selenite induced growth inhibition of the DLD1, RKO and HT-29 cells, with a marginal effect on the Caco2 cells. The Caco2 cells with mutant p53, failure to activate caspase-8, -9, -7 and -3 and with hypermethylated caspase-8 were resistant to 5-FU. Conversely, RKO cells expressing wildtype p53, proteolytically activated caspase-8, -9, -7 and -3 and unmethylated caspase-8 were more responsive to 5-FU and selenous acid-induced apoptosis. CONCLUSION: Combination treatment with selenous acid may offer an efficacious strategy to overcome 5-FU resistance in certain CRC cells.
BACKGROUND: The mechanisms that could explain the poor sensitivity to 5-FU in certain colorectal cancer (CRC) cells were investigated and whether or not cotreatment with low doses of selenium would offer a therapeutic benefit was explored. MATERIALS AND METHODS: Four CRC cell lines (Caco2, RKO, DLD1 andHT-29) with defined tumor signatures and seven different chemical forms of selenium were tested. RESULTS:5-FU partially inhibited the HT-29and RKO cells, but had a weak effect on the DLD1 and almost none on the Caco2 cells. Selenous acidandsodium selenite induced growth inhibition of the DLD1, RKO andHT-29 cells, with a marginal effect on the Caco2 cells. The Caco2 cells with mutant p53, failure to activate caspase-8, -9, -7 and -3and with hypermethylated caspase-8 were resistant to 5-FU. Conversely, RKO cells expressing wildtype p53, proteolytically activated caspase-8, -9, -7 and -3and unmethylated caspase-8 were more responsive to 5-FUandselenous acid-induced apoptosis. CONCLUSION: Combination treatment with selenous acid may offer an efficacious strategy to overcome 5-FU resistance in certain CRC cells.
Authors: J Y Douillard; D Cunningham; A D Roth; M Navarro; R D James; P Karasek; P Jandik; T Iveson; J Carmichael; M Alakl; G Gruia; L Awad; P Rougier Journal: Lancet Date: 2000-03-25 Impact factor: 79.321
Authors: Daniel B Longley; John Boyer; Wendy L Allen; Tariq Latif; Paul R Ferguson; Pamela J Maxwell; Ultan McDermott; Maria Lynch; D Paul Harkin; Patrick G Johnston Journal: Cancer Res Date: 2002-05-01 Impact factor: 12.701
Authors: D B Longley; P R Ferguson; J Boyer; T Latif; M Lynch; P Maxwell; D P Harkin; P G Johnston Journal: Clin Cancer Res Date: 2001-11 Impact factor: 12.531
Authors: Sang Rye Park; Kyoung Duk Lee; Uk Kyu Kim; Young Gi Gil; Kyu Seon Oh; Bong Soo Park; Gyoo Cheon Kim Journal: Yonsei Med J Date: 2010-09 Impact factor: 3.052