Acrofolione A and B, acetophenone dimers from Acronychia pendunculata, induce an apoptotic effect on human NALM-6 pre-B cell leukaemia cells
- J Pharm Pharmacol. 2019 Mar;71(3):348-361. doi: 10.1111/jphp.13035.
- 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.
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.