Acrofolione A and B, acetophenone dimers from Acronychia pendunculata, induce an apoptotic effect on human NALM-6 pre-B cell leukaemia cells

Takuya Matsui, Chihiro Ito, Ayumi Kato, Tian-Shung Wu, Masataka Itoigawa

Research output: Contribution to journalArticle

Abstract

Objectives: We investigated the apoptotic activities of acrofolione A (1) and B (2) isolated from Acronychia pedunculata against a human pre-B cell leukaemia cell line (NALM-6) to explore the apoptosis-related signalling molecules targeted by 1 and 2. Methods: The apoptosis effects of 1 and 2 in NALM-6 cells were investigated by TUNEL staining, annexin V, mitochondria membrane potential and caspase 3/7 activity. We carried out a protein array to explore the signalling molecules involved in apoptosis comprehensively. Key findings: Acrofolione A (1) suppressed the growth of NALM-6, K562 and HPB-ALL cells (IC 50 16.7 ± 1.9, 17.9 ± 0.3 and 10.1 ± 0.2 μm, respectively) more effectively than acrofolione B (2). Both compounds time-dependently increased the number of NALM-6 cells with abnormal nuclei, and increased the number of annexin V-positive cells and decreased the mitochondrial membrane potential of NALM-6 cells. Acrofolione A (1) markedly elevated caspase 3/7 activity and increased the number of TUNEL-positive cells. Cells treated with either compound showed enhanced expression of cleaved PARP and cleaved caspase 3 and 7, and reduced survivin protein levels. Conclusions: Acrofolione A (1) and B (2) may be useful in the treatment of various types of leukaemia.

Original languageEnglish (US)
Pages (from-to)348-361
Number of pages14
JournalJournal of Pharmacy and Pharmacology
Volume71
Issue number3
DOIs
StatePublished - Mar 1 2019

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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
Rutaceae
Caspase 7
Caspase 3
Annexin A5
In Situ Nick-End Labeling
Apoptosis
Thoracica
Protein Array Analysis
Mitochondrial Membrane Potential
acetophenone
Membrane Potentials
Mitochondria
Leukemia
Staining and Labeling
Cell Line

Keywords

  • Acronychia pedunculata
  • NALM-6
  • acrofolione A
  • acrofolione B
  • apoptosis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Acrofolione A and B, acetophenone dimers from Acronychia pendunculata, induce an apoptotic effect on human NALM-6 pre-B cell leukaemia cells. / Matsui, Takuya; Ito, Chihiro; Kato, Ayumi; Wu, Tian-Shung; Itoigawa, Masataka.

In: Journal of Pharmacy and Pharmacology, Vol. 71, No. 3, 01.03.2019, p. 348-361.

Research output: Contribution to journalArticle

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abstract = "Objectives: We investigated the apoptotic activities of acrofolione A (1) and B (2) isolated from Acronychia pedunculata against a human pre-B cell leukaemia cell line (NALM-6) to explore the apoptosis-related signalling molecules targeted by 1 and 2. Methods: The apoptosis effects of 1 and 2 in NALM-6 cells were investigated by TUNEL staining, annexin V, mitochondria membrane potential and caspase 3/7 activity. We carried out a protein array to explore the signalling molecules involved in apoptosis comprehensively. Key findings: Acrofolione A (1) suppressed the growth of NALM-6, K562 and HPB-ALL cells (IC 50 16.7 ± 1.9, 17.9 ± 0.3 and 10.1 ± 0.2 μm, respectively) more effectively than acrofolione B (2). Both compounds time-dependently increased the number of NALM-6 cells with abnormal nuclei, and increased the number of annexin V-positive cells and decreased the mitochondrial membrane potential of NALM-6 cells. Acrofolione A (1) markedly elevated caspase 3/7 activity and increased the number of TUNEL-positive cells. Cells treated with either compound showed enhanced expression of cleaved PARP and cleaved caspase 3 and 7, and reduced survivin protein levels. Conclusions: Acrofolione A (1) and B (2) may be useful in the treatment of various types of leukaemia.",
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