A potent apoptosis-inducing activity of a sesquiterpene lactone, arucanolide, in HL60 cells

A crucial role of apoptosis-inducing factor

Yoshihito Nakagawa, Munekazu Iinuma, Nobuyasu Matsuura, Kong Yi, Makoto Naoi, Toshihiro Nakayama, Yoshinori Nozawa, Yukihiro Akao

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Six main sesquiterpene lactones (germacranolides) from Calea urticifolia were evaluated for in vitro cytotoxicity against human tumor cell lines HL60 and SW480 cells. Among them, arucanolide and parthenolide displayed marked cytotoxicity against both cell lines. Arucanolide exhibited a low IC 50 in HL60 cells. The cytotoxic activity of arucanolide was observed at lower concentrations compared to that of parthenolide, which has been reported to be a typical and simple germacranolide. The activity was found to be mainly due to apoptosis that was assessed by morphological findings, DNA ladder formation (24-36h), and flow cytometric analysis in HL60 cells. Western blotting and an apoptosis inhibition assay using caspase inhibitors did not demonstrate the activation of any caspases tested. However, the mitochondrial membrane potential of HL60 cells was lost after 24-h treatment with arucanolide, and concurrently apoptosis-inducing factor (AIF) released from mitochondria was detected by Western blot analysis. The inactivation of nuclear factor-κB, which has been commonly shown in parthenolide-induced apoptosis, did not occur in arucanolide-induced apoptosis. Taken together, the findings presented here indicate that arucanolide induced marked apoptosis in HL60 cells mainly by dissipating mitochondrial membrane potential, which would trigger AIF-induced apoptosis.

Original languageEnglish
Pages (from-to)242-252
Number of pages11
JournalJournal of Pharmacological Sciences
Volume97
Issue number2
DOIs
Publication statusPublished - 01-02-2005

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Apoptosis Inducing Factor
Sesquiterpenes
HL-60 Cells
Lactones
Apoptosis
Mitochondrial Membrane Potential
Western Blotting
Caspase Inhibitors
Caspases
Tumor Cell Line
arucanolide
Mitochondria
Cell Line
DNA
parthenolide

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Nakagawa, Yoshihito ; Iinuma, Munekazu ; Matsuura, Nobuyasu ; Yi, Kong ; Naoi, Makoto ; Nakayama, Toshihiro ; Nozawa, Yoshinori ; Akao, Yukihiro. / A potent apoptosis-inducing activity of a sesquiterpene lactone, arucanolide, in HL60 cells : A crucial role of apoptosis-inducing factor. In: Journal of Pharmacological Sciences. 2005 ; Vol. 97, No. 2. pp. 242-252.
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A potent apoptosis-inducing activity of a sesquiterpene lactone, arucanolide, in HL60 cells : A crucial role of apoptosis-inducing factor. / Nakagawa, Yoshihito; Iinuma, Munekazu; Matsuura, Nobuyasu; Yi, Kong; Naoi, Makoto; Nakayama, Toshihiro; Nozawa, Yoshinori; Akao, Yukihiro.

In: Journal of Pharmacological Sciences, Vol. 97, No. 2, 01.02.2005, p. 242-252.

Research output: Contribution to journalArticle

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AU - Nakagawa, Yoshihito

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