The Inhibitory Effect of Dibutyryl Cyclic AMP on Docosahexaenoic Acid-Induced Apoptosis in HL-60 Cells through Activation of the Phosphatidylinositol-3 Kinase Pathway

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概要

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• Objective: Docosahexaenoic acid (DHA) is known as a chemopreventive substance for cancers. Previously we reported that DHA induces apoptosis in HL-60 cells. The aim of this study was to clarify the role of phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling during DHA-induced apoptosis in HL-60 cells. Methods: The inhibitory effects of dibutyryl cAMP (db-cAMP) or LY294002 (a specific inhibitor of the PI3-kinase/Akt pathway) on DHA-induced apoptosis in HL-60 cells were evaluated by the appearance of apoptosis, and from the activities of caspases (3 and 8), the phospholylation of Akt, and cleavage of Bid using DNA indexes, emzymatic measurement of fragmented substrates, and Western blotting, respectively. Results: The pre-incubation of db-cAMP reduced the activation of caspasses (3 and 8) during the occurrence of DHA-induced apoptosis in HL-60. However, the inhibition of PI3-kinase/Akt signaling by LY294002 resulted in recovery of the caspases’ activities, appearance of apoptotic cells, and cleavage of the Bid molecule when LY294002 was co-treated with db-cAMP before the occurrence of DHA-induced apoptosis in HL-60. It was also confirmed that LY294002 strongly inhibited phospholylation of Akt during db-cAMP induced-reduction of DHA-induced apoptosis in HL-60. Conclusion: We demonstrated that DHA-induced apoptosis was sensitive to the modulation of PI3-kinase activity by treatment with db-cAMP or LY294002. These results may provide new insights into the mechanisms of the anti-cancer activity of DHA.

• 日本衛生学会の論文
• 2005-07-01

著者

• MURATA Yoshiyuki

  Graduate School of Natural Science and Technology, Okayama University

• Murata Y

  Graduate School Of Natural Science And Technology Okayama University

• Miura Yoshie

  川崎医科大学 衛生学

• Miura Yoshie

  Dep. Of Biofunctional Chemistry Graduate School Of Natural Sci. And Technol. Okayama Univ.

• OTSUKI Takemi

  Department of Hygiene, Kawasaki Medical School

• Otsuki Takemi

  Department Of Hygiene Kawasaki Medical School

• Utsumi Kozo

  Institute Of Medical Science Kurashiki Medical Center

• MIURA Yoshie

  Graduate School of National Science and Technology, Okayama University

• TAKAHATA Kyoya

  Faculty of Agriculture, Okayama University

• TADA Mikiro

  Graduate School of National Science and Technology, Okayama University

• Masamoto Yukimitsu

  Graduate School Of Natural Science And Technology Okayama University

• Takahata K

  Faculty Of Agriculture Okayama University

• Takahata Kyoya

  Faculty Of Agriculture Okayama University

• Murata Yoshiyuki

  Graduate School Of Natural Science And Technology Okayama University

• Tada Mikiro

  Fac. Of Agriculture Okayama Univ.

• Murata Yoshiyuki

  Graduate School Of Natural Science And Technology Okayama Univ.

• Murata Yoshiyuki

  Graduate School Of Natural Sci. And Technol. Okayama Univ.

• MURATA Yoshiyuki

  Graduate School of National Science and Technology, Okayama University

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