The inhibitory effect of dibutyryl cyclic AMP on docosahexaenoic acid-induced apoptosis in HL-60 cells through activation of the phosphatidylinositol-3 kinase pathway

Yoshie Miura, Yoshiyuki Murata, Kozo Utsumi, Kyoya Takahata, Mikiro Tada, Takemi Otsuki

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)184-189
Number of pages6
JournalEnvironmental Health and Preventive Medicine
Volume10
Issue number4
DOIs
Publication statusPublished - Jul 2005

Fingerprint

Phosphatidylinositol 3-Kinase
Bucladesine
Docosahexaenoic Acids
HL-60 Cells
Cell death
Chemical activation
Apoptosis
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Acids
Cyclic AMP
Caspase 8
Caspases
Caspase 3
Neoplasms
DNA
Western Blotting
Cells
Modulation

Keywords

  • Akt
  • Apoptosis
  • Docosahexaenoic acid
  • HL-60 cells
  • Phosphatidylinositol-3 kinase pathway

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Pollution

Cite this

The inhibitory effect of dibutyryl cyclic AMP on docosahexaenoic acid-induced apoptosis in HL-60 cells through activation of the phosphatidylinositol-3 kinase pathway. / Miura, Yoshie; Murata, Yoshiyuki; Utsumi, Kozo; Takahata, Kyoya; Tada, Mikiro; Otsuki, Takemi.

In: Environmental Health and Preventive Medicine, Vol. 10, No. 4, 07.2005, p. 184-189.

Research output: Contribution to journalArticle

@article{feb03fbc77d24ee5858d6d776bdf5946,
title = "The inhibitory effect of dibutyryl cyclic AMP on docosahexaenoic acid-induced apoptosis in HL-60 cells through activation of the phosphatidylinositol-3 kinase pathway",
abstract = "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.",
keywords = "Akt, Apoptosis, Docosahexaenoic acid, HL-60 cells, Phosphatidylinositol-3 kinase pathway",
author = "Yoshie Miura and Yoshiyuki Murata and Kozo Utsumi and Kyoya Takahata and Mikiro Tada and Takemi Otsuki",
year = "2005",
month = "7",
doi = "10.1265/ehpm.10.184",
language = "English",
volume = "10",
pages = "184--189",
journal = "Environmental Health and Preventive Medicine",
issn = "1342-078X",
publisher = "Springer Japan",
number = "4",

}

TY - JOUR

T1 - The inhibitory effect of dibutyryl cyclic AMP on docosahexaenoic acid-induced apoptosis in HL-60 cells through activation of the phosphatidylinositol-3 kinase pathway

AU - Miura, Yoshie

AU - Murata, Yoshiyuki

AU - Utsumi, Kozo

AU - Takahata, Kyoya

AU - Tada, Mikiro

AU - Otsuki, Takemi

PY - 2005/7

Y1 - 2005/7

N2 - 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.

AB - 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.

KW - Akt

KW - Apoptosis

KW - Docosahexaenoic acid

KW - HL-60 cells

KW - Phosphatidylinositol-3 kinase pathway

UR - http://www.scopus.com/inward/record.url?scp=24944525304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24944525304&partnerID=8YFLogxK

U2 - 10.1265/ehpm.10.184

DO - 10.1265/ehpm.10.184

M3 - Article

VL - 10

SP - 184

EP - 189

JO - Environmental Health and Preventive Medicine

JF - Environmental Health and Preventive Medicine

SN - 1342-078X

IS - 4

ER -