Background: Pterostilbene (PTER) is a dimethylated analog of the phenolic phytoalexin, resveratrol, with higher anticancer activity in various tumors. Herein, the molecular mechanisms by which PTER exerts its anticancer effects against acute myeloid leukemia (AML) cells were investigated. Methodology and Principal Findings: Results showed that PTER suppressed cell proliferation in various AML cell lines. PTER-induced G0/G1-phase arrest occurred when expressions of cyclin D3 and cyclin-dependent kinase (CDK)2/6 were inhibited. PTER-induced cell apoptosis occurred through activation of caspases-8-9/-3, and a mitochondrial membrane permeabilization (MMP)-dependent pathway. Moreover, treatment of HL-60 cells with PTER induced sustained activation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK)1/2, and inhibition of both MAPKs by their specific inhibitors significantly abolished the PTER-induced activation of caspases-8/-9/-3. Of note, PTER-induced cell growth inhibition was only partially reversed by the caspase-3-specific inhibitor, Z-DEVE-FMK, suggesting that this compound may also act through a caspase-independent pathway. Interestingly, we also found that PTER promoted disruption of lysosomal membrane permeabilization (LMP) and release of activated cathepsin B. Conclusion: Taken together, our results suggest that PTER induced HL-60 cell death via MAPKs-mediated mitochondria apoptosis pathway and loss of LMP might be another cause for cell apoptosis induced by PTER.
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
Hsiao, P. C., Chou, Y. E., Tan, P., Lee, W-J., Yang, S. F., Chow, J-M., Chen, H. Y., Lin, C-H., Lee, L-M., & Chien, M-H. (2014). Pterostilbene simultaneously induced G0/G1-phase arrest and MAPK-mediated mitochondrial-derived apoptosis in human acute myeloid leukemia cell lines. PLoS One, 9(8), [e105342]. https://doi.org/10.1371/journal.pone.0105342