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 language | English |
|---|---|
| Pages (from-to) | 348-361 |
| Number of pages | 14 |
| Journal | Journal of Pharmacy and Pharmacology |
| Volume | 71 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2019 Mar 1 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmaceutical Science
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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 journal › Article
TY - JOUR
T1 - Acrofolione A and B, acetophenone dimers from Acronychia pendunculata, induce an apoptotic effect on human NALM-6 pre-B cell leukaemia cells
AU - Matsui, Takuya
AU - Ito, Chihiro
AU - Kato, Ayumi
AU - Wu, Tian-Shung
AU - Itoigawa, Masataka
PY - 2019/3/1
Y1 - 2019/3/1
N2 - 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.
AB - 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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U2 - 10.1111/jphp.13035
DO - 10.1111/jphp.13035
M3 - Article
VL - 71
SP - 348
EP - 361
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 3
ER -