Possible Involvement of p38 in Mechanisms Underlying Acceleration of Proliferation by 15-Deoxy-Δ12,14-prostaglandin J2 and the Precursors in Leukemia Cell Line THP-1

• Azuma Yasutaka

  Department of Pharmacology, Osaka Dental University

• Watanabe Kyoko

  Department of Pediatric Dentistry, Osaka Dental University

• Date Masataka

  Department of Pharmacology, Osaka Dental University

• Daito Michiharu

  Department of Pediatric Dentistry, Osaka Dental University

• Ohura Kiyoshi

  Department of Pharmacology, Osaka Dental University

書誌事項

タイトル別名

• Possible Involvement of p38 in Mechanisms Underlying Acceleration of Proliferation by 15-Deoxy-.DELTA.12,14-prostaglandin J2 and the Precursors in Leukemia Cell Line THP-1
• Possible Involvement of p38 in Mechanisms Underlying Acceleration of Proliferation by 15 Deoxy デルタ 12 14 prostaglandin J2 and the Precursors in Leukemia Cell Line THP 1

抄録

15-Deoxy-Δ^12,14-prostaglandin J₂ (15dPGJ₂), which is a ligand for peroxisome proliferator-activated receptor γ (PPARγ), induced apoptosis of several human tumors including gastric, lung, colon, prostate, and breast. However, the role of PPARγ signals in other types of cancer cells (e.g., leukemia) except solid cancer cells is still unclear. The aim of this study is to evaluate the ability of 15dPGJ₂ to modify the proliferation of the human leukemia cell line THP-1. 15dPGJ₂ at 5 μM stimulated the proliferation in THP-1 at 24 to 72 h after incubation. In contrast, 15dPGJ₂ at concentrations above 10 μM inhibited the proliferation through the induction of apoptosis. PGD₂, PGJ₂, and Δ¹²-PGJ₂ (ΔPGJ₂), precursors of 15dPGJ₂, had similar proliferative effects at lower concentrations, whereas they induced apoptosis at high concentrations. 15dPGJ₂ and three precursors failed to induce the differentiation in THP-1 as assessed by using the differentiation marker CD11b. FACScan analysis revealed that PGD₂ at 5 μM, PGJ₂ at 1 μM, ΔPGJ₂ at 1 μM and 15dPGJ₂ at 5 μM all accelerated cell cycle progression in THP-1. Immunoblotting analysis revealed that PGD₂ at 5 μM and 15dPGJ₂ at 5 μM inhibited the expression of phospho-p38, phospho-MKK3/MKK6, and phospho-ATF-2, and the expression of Cdk inhibitors including p18, p21, and p27 in THP-1. In contrast, PGJ₂ at 1 μM and ΔPGJ₂ at 1 μM did not affect their expressions. These results suggest that 15dPGJ₂ and PGD₂ may, through inactivation of the p38 mitogen-activated protein kinase pathway, inhibit the expression of Cdk inhibitors, leading to acceleration of the THP-1 proliferation.<br>

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 94 (3), 261-270, 2004

  公益社団法人 日本薬理学会

キーワード

• THP-1
• proliferation
• 15-deoxy-Δ^12,14-prostaglandin J₂
• prostaglandin D₂
• p38

詳細情報

• CRID: 1390001205177127808
• NII論文ID: 130000073845
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.94.261
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 6890234
• PubMed: 15037811
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I6890234
• Web Site: https://search.jamas.or.jp/link/ui/2004230673
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• 抄録ライセンスフラグ: 使用不可