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    Article

    Kayeassamin A Isolated from the Flower of Mammea siamensis Triggers Apoptosis by Activating Caspase-3/-8 in HL-60 Human Leukemia Cells

    Takuhiro Uto1, Nguyen Huu Tung1,2, Pinjutha Thongjankaew3, Sorasak Lhieochaiphant4, Yukihiro Shoyama1★★ Corresponding author

    1. 1Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo, Nagasaki 859-3298, Japan
    2. 2School of Medicine and Pharmacy, Vietnam National University, Hanoi, Vietnam
    3. 3Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002
    4. 4Faculty of Pharmacy, Payap University, Muang, Chiang Mai 50000, Thailand

    CORRESPONDENCE

    Yukihiro Shoyama

    Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japan.

    shoyama@niu.ac.jp

    Volume 8, Issue 4 · pp. 244–248 · PUBLISHED Oct-Dec 2016 · DOI: 10.4103/0974-8490.188884

    View on Pharmacogn. Res. original site ↗

    ABSTRACT

    Background Mammea siamensiŝ(Miq.) T. Anders. is used as a medicinal plant in Thailand and has several traditional therapeutic properties. In a previous study, we isolated eight compounds from the ˚ower of M. siamensis and demonstrated that kayeassamin A~(KA) exhibited potent antiproliferative activity against human leukemia and stomach cancer cell lines. Objective In this study, we investigated the effect of KA on cell viability and apoptotic mechanisms in HL-60 human leukemia cells. Materials and Methods Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Nuclear morphology and DNA fragmentation were observed using Hoechst 33258 staining and agarose gel electrophoresis, respectively. The sub-G1 phase of cells was analyzed by ˚ow cytometry after the cellular DNA had been stained with propidium iodide. The protein levels of poly~ (ADP-ribose) polymerase~ (PARP) and caspases were determined by Western blotting. Results KA exhibited a signi˛cant cytotoxic effect in a dose-~ and time-dependent manner, and induced chromatin condensation, DNA fragmentation, and sub-G1 phase DNA content, known as molecular events associated with the induction of apoptosis. In addition, KA strongly induced the activation of PARP and caspase-3 and~-8, with weak caspase-9 activation. Furthermore, KA-induced DNA fragmentation was abolished by pretreatment with z-VAD-FMK (a broad caspase inhibitor), z-DEVD-FMK (a caspase-3 inhibitor), and z-IETD-FMK~ (a caspase-8 inhibitor), but not by z-LEHD-FMK (a caspase-9 inhibitor) pretreatment. Conclusion These results indicate that KA triggers apoptotic cell death by activation of caspase-3 and~-8 in HL-60~cells.

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      Uto, T., Tung, N. H., Thongjankaew, P., Lhieochaiphant, S., & Shoyama, Y. (2016). Kayeassamin A Isolated from the Flower of Mammea siamensis Triggers Apoptosis by Activating Caspase-3/-8 in HL-60 Human Leukemia Cells. Pharmacognosy Research, 8(4), 244–248. https://doi.org/10.4103/0974-8490.188884