Diclofenac, a non-steroidal anti-inflammatory drug, suppresses apoptosis induced by endoplasmic reticulum stresses by inhibiting caspase signaling

Takao Yamazaki, Masakazu Muramoto, Tomoya Oe, Noriyuki Morikawa, Osamu Okitsu, Takeyuki Nagashima, Shintaro Nishimura, Yoshiki Katayama, Yasuhiro Kita

研究成果: ジャーナルへの寄稿記事

35 引用 (Scopus)

抄録

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used in the treatment of inflammation and pain. In many reports, NSAIDs have induced apoptosis in a variety of cell lines such as colon cancer cells. On the other hand, more recently a few reports have found that NSAIDs protect against apoptosis. Here we investigate endoplasmic reticulum (ER)-stress-induced apoptosis of neuronal cells. The aim of this study is to examine the involvement of NSAIDs, in particular diclofenac, on ER-stress-induced apoptosis of human neuroblastoma SH-SY5Y cells. Diclofenac significantly suppressed SH-SY5Y cell death induced by two types of ER-stress-inducing agents: thapsigargin, an inhibitor of Ca2+-ATPase on the endoplasmic reticulum membrane, and tunicamycin, a glycosylation blocker. Other NSAIDs, such as indomethacin, ibuprofen, aspirin, and ketoprofen, also suppressed ER-stress-induced SH-SY5Y cell death. The dose-dependent anti-apoptotic effect of diclofenac did not correlate with the reduction of prostaglandin release. Administration of prostaglandin E2, which was a primary product of arachidonic metabolism, showed no effects against anti-apoptotic effects produced by diclofenac. Thapsigargin and tunicamycin each significantly activated caspase-3, -9, and -2 in the intrinsic apoptotic pathway in SH-SY5Y cells. Diclofenac suppressed the activation of caspases induced by both ER stresses. Thapsigargin and tunicamycin decreased the mitochondrial membrane potential in SH-SY5Y cells. Diclofenac suppressed the mitochondrial depolarization induced by both ER stresses. Diclofenac inhibited ER-stress-induced apoptosis of SH-SY5Y cells by suppressing the activation of caspases in the intrinsic apoptotic pathway. This is the first report to find that diclofenac has protective effects against ER-stress-induced apoptosis.

元の言語英語
ページ(範囲)558-567
ページ数10
ジャーナルNeuropharmacology
50
発行部数5
DOI
出版物ステータス出版済み - 4 1 2006

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Endoplasmic Reticulum Stress
Diclofenac
Caspases
Anti-Inflammatory Agents
Apoptosis
Tunicamycin
Pharmaceutical Preparations
Thapsigargin
Cell Death
Ketoprofen
Calcium-Transporting ATPases
Caspase 9
Mitochondrial Membrane Potential
Ibuprofen
Neuroblastoma
Glycosylation
Dinoprostone
Indomethacin
Caspase 3
Endoplasmic Reticulum

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cellular and Molecular Neuroscience

これを引用

Diclofenac, a non-steroidal anti-inflammatory drug, suppresses apoptosis induced by endoplasmic reticulum stresses by inhibiting caspase signaling. / Yamazaki, Takao; Muramoto, Masakazu; Oe, Tomoya; Morikawa, Noriyuki; Okitsu, Osamu; Nagashima, Takeyuki; Nishimura, Shintaro; Katayama, Yoshiki; Kita, Yasuhiro.

:: Neuropharmacology, 巻 50, 番号 5, 01.04.2006, p. 558-567.

研究成果: ジャーナルへの寄稿記事

Yamazaki, Takao ; Muramoto, Masakazu ; Oe, Tomoya ; Morikawa, Noriyuki ; Okitsu, Osamu ; Nagashima, Takeyuki ; Nishimura, Shintaro ; Katayama, Yoshiki ; Kita, Yasuhiro. / Diclofenac, a non-steroidal anti-inflammatory drug, suppresses apoptosis induced by endoplasmic reticulum stresses by inhibiting caspase signaling. :: Neuropharmacology. 2006 ; 巻 50, 番号 5. pp. 558-567.
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abstract = "Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used in the treatment of inflammation and pain. In many reports, NSAIDs have induced apoptosis in a variety of cell lines such as colon cancer cells. On the other hand, more recently a few reports have found that NSAIDs protect against apoptosis. Here we investigate endoplasmic reticulum (ER)-stress-induced apoptosis of neuronal cells. The aim of this study is to examine the involvement of NSAIDs, in particular diclofenac, on ER-stress-induced apoptosis of human neuroblastoma SH-SY5Y cells. Diclofenac significantly suppressed SH-SY5Y cell death induced by two types of ER-stress-inducing agents: thapsigargin, an inhibitor of Ca2+-ATPase on the endoplasmic reticulum membrane, and tunicamycin, a glycosylation blocker. Other NSAIDs, such as indomethacin, ibuprofen, aspirin, and ketoprofen, also suppressed ER-stress-induced SH-SY5Y cell death. The dose-dependent anti-apoptotic effect of diclofenac did not correlate with the reduction of prostaglandin release. Administration of prostaglandin E2, which was a primary product of arachidonic metabolism, showed no effects against anti-apoptotic effects produced by diclofenac. Thapsigargin and tunicamycin each significantly activated caspase-3, -9, and -2 in the intrinsic apoptotic pathway in SH-SY5Y cells. Diclofenac suppressed the activation of caspases induced by both ER stresses. Thapsigargin and tunicamycin decreased the mitochondrial membrane potential in SH-SY5Y cells. Diclofenac suppressed the mitochondrial depolarization induced by both ER stresses. Diclofenac inhibited ER-stress-induced apoptosis of SH-SY5Y cells by suppressing the activation of caspases in the intrinsic apoptotic pathway. This is the first report to find that diclofenac has protective effects against ER-stress-induced apoptosis.",
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T1 - Diclofenac, a non-steroidal anti-inflammatory drug, suppresses apoptosis induced by endoplasmic reticulum stresses by inhibiting caspase signaling

AU - Yamazaki, Takao

AU - Muramoto, Masakazu

AU - Oe, Tomoya

AU - Morikawa, Noriyuki

AU - Okitsu, Osamu

AU - Nagashima, Takeyuki

AU - Nishimura, Shintaro

AU - Katayama, Yoshiki

AU - Kita, Yasuhiro

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Y1 - 2006/4/1

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