Takuya Matsui1,2, Chihiro Ito2, Ayumi Kato2, Tian-Shung Wu3, Masataka Itoigawa4. 1. Department of Physiology, Aichi Medical University, Nagakute, Aichi, Japan. 2. Faculty of Pharmacy, Meijo University, Nagoya, Aichi, Japan. 3. Department of Chemistry, National Cheng Kung University, Tainan, Taiwan. 4. School of Sports and Health Science, Tokai Gakuen University, Miyoshi, Aichi, Japan.
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 (IC50 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.
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 (IC50 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.
Authors: Kim-Thao Le; Jan J Bandolik; Matthias U Kassack; Kenneth R Wood; Claudia Paetzold; Marc S Appelhans; Claus M Passreiter Journal: Molecules Date: 2021-01-28 Impact factor: 4.411