Role of caspases in 5-FU and selenium-induced growth inhibition of colorectal cancer cells

Aye Aye Thant, Yanyuan Wu, Jane Lee, Dhruva Kumar Mishra, Heather Garcia, H. Phillip Koeffler, Jaydutt V. Vadgama

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Background: The mechanisms that could explain the poor sensitivity to 5-FU in certain colorectal cancer (CRC) cells were investigated and whether or not co-treatment 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 wild-type 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.

Original languageEnglish (US)
Pages (from-to)3579-3592
Number of pages14
JournalAnticancer Research
Volume28
Issue number6 A
StatePublished - Nov 2008

Keywords

  • 5-FU
  • Apoptosis
  • Caspases
  • Colorectal cancer
  • Selenium
  • Selenous acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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