Induction of Apoptosis in Leukemic Cells by Homovanillic Acid Derivative, Capsaicin, through Oxidative Stress

Implication of Phosphorylation of p53 at Ser-15 Residue by Reactive Oxygen Species

Keisuke Ito, Tomonori Nakazato, Kenji Yamato, Yoshitaka Miyakawa, Taketo Yamada, Nobumichi Hozumi, Kaoru Segawa, Yasuo Ikeda, Masahiro Kizaki

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

Capsaicin (N-vanillyl-8-methyl-1-nonenamide) is a homovanillic acid derivative found in pungent fruits. Several investigators have reported the ability of capsaicin to inhibit events associated with the promotion of cancer. However, the effects of capsaicin on human leukemic cells have never been investigated. We investigated the effects of capsaicin on leukemic cells in vitro and in vivo and further examined the molecular mechanisms of capsaicin-induced apoptosis in myeloid leukemic cells. Capsaicin suppressed the growth of leukemic cells, but not normal bone marrow mononuclear cells, via induction of G0-G1 phase cell cycle arrest and apoptosis. Capsaicin-induced apoptosis was in association with the elevation of intracellular reactive oxygen species production. Interestingly, capsaicin-sensitive leukemic cells were possessed of wild-type p53, resulting in the phosphorylation of p53 at the Ser-15 residue by the treatment of capsaicin. Abrogation of p53 expression by the antisense oligonucleotides significantly attenuated capsaicin-induced cell cycle arrest and apoptosis. Pretreatment with the antioxidant N-acetyl-L-cystein and catalase, but not superoxide dismutase, completely inhibited capsaicin-induced apoptosis by inhibiting phosphorylation of Ser-15 residue of p53. Moreover, capsaicin effectively inhibited tumor growth and induced apoptosis in vivo using NOD/SCID mice with no toxic effects. We conclude that capsaicin has potential as a novel therapeutic agent for the treatment of leukemia.

Original languageEnglish
Pages (from-to)1071-1078
Number of pages8
JournalCancer Research
Volume64
Issue number3
DOIs
Publication statusPublished - 2004 Feb 1

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Homovanillic Acid
Capsaicin
Reactive Oxygen Species
Oxidative Stress
Phosphorylation
Apoptosis
G1 Phase Cell Cycle Checkpoints
Cell Cycle Resting Phase
Inbred NOD Mouse
SCID Mice
Antisense Oligonucleotides
Poisons
G1 Phase
Myeloid Cells
Growth
Cell Cycle Checkpoints
Bone Marrow Cells
Catalase
Superoxide Dismutase
Fruit

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Induction of Apoptosis in Leukemic Cells by Homovanillic Acid Derivative, Capsaicin, through Oxidative Stress : Implication of Phosphorylation of p53 at Ser-15 Residue by Reactive Oxygen Species. / Ito, Keisuke; Nakazato, Tomonori; Yamato, Kenji; Miyakawa, Yoshitaka; Yamada, Taketo; Hozumi, Nobumichi; Segawa, Kaoru; Ikeda, Yasuo; Kizaki, Masahiro.

In: Cancer Research, Vol. 64, No. 3, 01.02.2004, p. 1071-1078.

Research output: Contribution to journalArticle

Ito, Keisuke ; Nakazato, Tomonori ; Yamato, Kenji ; Miyakawa, Yoshitaka ; Yamada, Taketo ; Hozumi, Nobumichi ; Segawa, Kaoru ; Ikeda, Yasuo ; Kizaki, Masahiro. / Induction of Apoptosis in Leukemic Cells by Homovanillic Acid Derivative, Capsaicin, through Oxidative Stress : Implication of Phosphorylation of p53 at Ser-15 Residue by Reactive Oxygen Species. In: Cancer Research. 2004 ; Vol. 64, No. 3. pp. 1071-1078.
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