The 15-lipoxygenase-1 expression may enhance the sensitivity to non-steroidal anti-inflammatory drug-induced apoptosis in colorectal cancers from patients who are treated with the compounds

Masahiro Yoshinaga, Hiroyuki Murao, Yosuke Kitamura, Koutaro Koga, Satoru Tsuruta, Hisato Igarashi, Kazuhiko Nakamura, Ryoichi Takayanagi

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Abstract

Background and Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) can prevent colorectal cancer (CRC), but their effect is limited. Recent studies have shown the involvement of 15-lipoxygenase-1 (15-LOX-1) in NSAID-induced apoptosis in colorectal carcinoma cells. We evaluate whether 15-LOX-1 expression influences the sensitivity of NSAID-induced apoptosis in CRCs. Methods: In 22 CRC surgical samples from NSAID users who had been constant for more than 5 years and 28 CRC surgical samples from NSAID non-users, the expressions of 15-LOX-1, cyclooxygenase-2 (COX-2), beta-catenin, and p53 were analyzed using immunohistochemistry. TUNEL assay was also performed for samples. The effects of the transient transfection of 15-LOX-1 cDNA on indomethacin-induced apoptosis were certified in HCT-116 cells. The effects of adding 13-S- hydroxyoctadecadinoic acid (13-S-HODE) on indomethacin-induced apoptosis were also examined in HCT-116 cells. The levels of apoptosis were determined by the analysis of the floating-cells ratio and DNA gel electrophoresis. Results: The expression of 15-LOX-1 on CRCs from NSAID users was significantly decreased compared with those from NSAID non-users; however, the expressions of other molecules were not significantly different between two groups. The levels of TUNEL scoring in samples from NSAID users were similar to those from NSAID non-users. Indomethacin (100 μM) induced less apoptosis in mocked cells, whereas the same concentrations of indomethacin enhanced the level of apoptosis in 15-LOX-1-transfected cells. 13-S-HODE also increased the level of indomethacin-induced apoptosis in cells. Conclusion: Results suggest that 15-LOX-1 expression may be one of the mechanisms which enhance the sensitivity to NSAID-induced apoptosis in CRCs from patients who are treated with the compounds.

Original languageEnglish
Pages (from-to)2324-2329
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume22
Issue number12
DOIs
Publication statusPublished - Dec 2007

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Arachidonate 15-Lipoxygenase
Lipoxygenase
Colorectal Neoplasms
Anti-Inflammatory Agents
Apoptosis
Drug Users
Indomethacin
Pharmaceutical Preparations
HCT116 Cells
In Situ Nick-End Labeling
Acids
beta Catenin
Cyclooxygenase 2
Transfection
Electrophoresis
Complementary DNA
Gels
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

The 15-lipoxygenase-1 expression may enhance the sensitivity to non-steroidal anti-inflammatory drug-induced apoptosis in colorectal cancers from patients who are treated with the compounds. / Yoshinaga, Masahiro; Murao, Hiroyuki; Kitamura, Yosuke; Koga, Koutaro; Tsuruta, Satoru; Igarashi, Hisato; Nakamura, Kazuhiko; Takayanagi, Ryoichi.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 22, No. 12, 12.2007, p. 2324-2329.

Research output: Contribution to journalArticle

Yoshinaga, Masahiro ; Murao, Hiroyuki ; Kitamura, Yosuke ; Koga, Koutaro ; Tsuruta, Satoru ; Igarashi, Hisato ; Nakamura, Kazuhiko ; Takayanagi, Ryoichi. / The 15-lipoxygenase-1 expression may enhance the sensitivity to non-steroidal anti-inflammatory drug-induced apoptosis in colorectal cancers from patients who are treated with the compounds. In: Journal of Gastroenterology and Hepatology (Australia). 2007 ; Vol. 22, No. 12. pp. 2324-2329.
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abstract = "Background and Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) can prevent colorectal cancer (CRC), but their effect is limited. Recent studies have shown the involvement of 15-lipoxygenase-1 (15-LOX-1) in NSAID-induced apoptosis in colorectal carcinoma cells. We evaluate whether 15-LOX-1 expression influences the sensitivity of NSAID-induced apoptosis in CRCs. Methods: In 22 CRC surgical samples from NSAID users who had been constant for more than 5 years and 28 CRC surgical samples from NSAID non-users, the expressions of 15-LOX-1, cyclooxygenase-2 (COX-2), beta-catenin, and p53 were analyzed using immunohistochemistry. TUNEL assay was also performed for samples. The effects of the transient transfection of 15-LOX-1 cDNA on indomethacin-induced apoptosis were certified in HCT-116 cells. The effects of adding 13-S- hydroxyoctadecadinoic acid (13-S-HODE) on indomethacin-induced apoptosis were also examined in HCT-116 cells. The levels of apoptosis were determined by the analysis of the floating-cells ratio and DNA gel electrophoresis. Results: The expression of 15-LOX-1 on CRCs from NSAID users was significantly decreased compared with those from NSAID non-users; however, the expressions of other molecules were not significantly different between two groups. The levels of TUNEL scoring in samples from NSAID users were similar to those from NSAID non-users. Indomethacin (100 μM) induced less apoptosis in mocked cells, whereas the same concentrations of indomethacin enhanced the level of apoptosis in 15-LOX-1-transfected cells. 13-S-HODE also increased the level of indomethacin-induced apoptosis in cells. Conclusion: Results suggest that 15-LOX-1 expression may be one of the mechanisms which enhance the sensitivity to NSAID-induced apoptosis in CRCs from patients who are treated with the compounds.",
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T1 - The 15-lipoxygenase-1 expression may enhance the sensitivity to non-steroidal anti-inflammatory drug-induced apoptosis in colorectal cancers from patients who are treated with the compounds

AU - Yoshinaga, Masahiro

AU - Murao, Hiroyuki

AU - Kitamura, Yosuke

AU - Koga, Koutaro

AU - Tsuruta, Satoru

AU - Igarashi, Hisato

AU - Nakamura, Kazuhiko

AU - Takayanagi, Ryoichi

PY - 2007/12

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N2 - Background and Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) can prevent colorectal cancer (CRC), but their effect is limited. Recent studies have shown the involvement of 15-lipoxygenase-1 (15-LOX-1) in NSAID-induced apoptosis in colorectal carcinoma cells. We evaluate whether 15-LOX-1 expression influences the sensitivity of NSAID-induced apoptosis in CRCs. Methods: In 22 CRC surgical samples from NSAID users who had been constant for more than 5 years and 28 CRC surgical samples from NSAID non-users, the expressions of 15-LOX-1, cyclooxygenase-2 (COX-2), beta-catenin, and p53 were analyzed using immunohistochemistry. TUNEL assay was also performed for samples. The effects of the transient transfection of 15-LOX-1 cDNA on indomethacin-induced apoptosis were certified in HCT-116 cells. The effects of adding 13-S- hydroxyoctadecadinoic acid (13-S-HODE) on indomethacin-induced apoptosis were also examined in HCT-116 cells. The levels of apoptosis were determined by the analysis of the floating-cells ratio and DNA gel electrophoresis. Results: The expression of 15-LOX-1 on CRCs from NSAID users was significantly decreased compared with those from NSAID non-users; however, the expressions of other molecules were not significantly different between two groups. The levels of TUNEL scoring in samples from NSAID users were similar to those from NSAID non-users. Indomethacin (100 μM) induced less apoptosis in mocked cells, whereas the same concentrations of indomethacin enhanced the level of apoptosis in 15-LOX-1-transfected cells. 13-S-HODE also increased the level of indomethacin-induced apoptosis in cells. Conclusion: Results suggest that 15-LOX-1 expression may be one of the mechanisms which enhance the sensitivity to NSAID-induced apoptosis in CRCs from patients who are treated with the compounds.

AB - Background and Aim: Non-steroidal anti-inflammatory drugs (NSAIDs) can prevent colorectal cancer (CRC), but their effect is limited. Recent studies have shown the involvement of 15-lipoxygenase-1 (15-LOX-1) in NSAID-induced apoptosis in colorectal carcinoma cells. We evaluate whether 15-LOX-1 expression influences the sensitivity of NSAID-induced apoptosis in CRCs. Methods: In 22 CRC surgical samples from NSAID users who had been constant for more than 5 years and 28 CRC surgical samples from NSAID non-users, the expressions of 15-LOX-1, cyclooxygenase-2 (COX-2), beta-catenin, and p53 were analyzed using immunohistochemistry. TUNEL assay was also performed for samples. The effects of the transient transfection of 15-LOX-1 cDNA on indomethacin-induced apoptosis were certified in HCT-116 cells. The effects of adding 13-S- hydroxyoctadecadinoic acid (13-S-HODE) on indomethacin-induced apoptosis were also examined in HCT-116 cells. The levels of apoptosis were determined by the analysis of the floating-cells ratio and DNA gel electrophoresis. Results: The expression of 15-LOX-1 on CRCs from NSAID users was significantly decreased compared with those from NSAID non-users; however, the expressions of other molecules were not significantly different between two groups. The levels of TUNEL scoring in samples from NSAID users were similar to those from NSAID non-users. Indomethacin (100 μM) induced less apoptosis in mocked cells, whereas the same concentrations of indomethacin enhanced the level of apoptosis in 15-LOX-1-transfected cells. 13-S-HODE also increased the level of indomethacin-induced apoptosis in cells. Conclusion: Results suggest that 15-LOX-1 expression may be one of the mechanisms which enhance the sensitivity to NSAID-induced apoptosis in CRCs from patients who are treated with the compounds.

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