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
N1 - Funding Information:
This work was supported by JSPS KAKENHI grant number JP17K08353.
Funding Information:
This work was supported by JSPS KAKENHI grant number JP17K08353. We thank Prof. C. S. Kouh of National Cheng-Kung University for collecting, processing and posting the material. We also thank Prof. Satoru Masubuchi, Prof. Kazuhiro Yoshikawa and Dr. Akinobu Ota at Aichi Medical University for advice about this study. We thank the Central Research Laboratories of Aichi Medical University for support in cell analysis.
Publisher Copyright:
© 2018 Royal Pharmaceutical Society
PY - 2019/3
Y1 - 2019/3
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
C2 - 30362134
AN - SCOPUS:85055467027
VL - 71
SP - 348
EP - 361
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 3
ER -