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    Article

    In vitro Cytotoxic Activities and Molecular Mechanisms of Angelica shikokiana Extract and its Isolated Compounds

    Amira Mira1,2, Kuniyoshi Shimizu1★★ Corresponding author

    1. 1Department of Agro-environmental Sciences, Division of Systematic Forest and Forest Products Sciences, Faculty of Agriculture, Graduate School of Kyushu University, Hakozaki 6-10-1, Fukuoka 〒812-8581, Japan.
    2. 2Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.

    CORRESPONDENCE

    Kuniyoshi Shimizu

    Department of Agro-environmental Sciences, Division of Systematic Forest and Forest Products Sciences, Faculty of Agriculture, Graduate School of Kyushu University, Hakozaki 6-10-1, Fukuoka 〒812-8581, Japan.

    shimizu@agr.kyushu-u.ac.jp

    Volume 11, Issue 44s3 · pp. 564–569 · PUBLISHED 2015 · DOI: 10.4103/0973-1296.172962

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    Background: Angelica shikokiana is a Japanese medicinal herb that is included among food and drug preparations protecting against cancer; however, there is no previous report about the cytotoxicity of A. shikokiana or its bioactive compounds. Objective: This study was designed to investigate the cytotoxic activities of A. shikokiana methanol extract (AME) and its isolated compounds and to identify the molecular mechanisms of the cytotoxicity. Materials and Methods: Cytotoxicity and selectivity was investigated by measuring the IC50 values on five cancer cell lines; human hepatocellular carcinoma, rhabdomyosarcoma (RD), colorectal carcinoma, human epithelioma and human breast adenocarcinoma and one normal cell line; human lung fibroblasts. The effects on tubulin polymerization and histone deacetylase 8 (HDAC8), were examined to determine the mechanism of cytotoxicity. Docking study was designed to examine the binding affinity to the target molecules. Results: Methanol extract and some of its isolated coumarins and flavonoids showed potent, selective cytotoxicity against cancer cell lines. AME and all isolated compounds inhibited tubulin polymerization. Angelicin and kaempferol-3-O-rutinoside were the most active compounds. Phenolic compounds and furanocoumarins showed binding affinity to colchicine binding site rather than the vinblastine binding site of tubulin microtubules. On the other side, quercetin, kaempferol, luteolin, chlorogenic acid, and methyl chlorogenate exhibited the strongest activity against HDAC8 and the highest affinity to trichostatin A binding site. Conclusion: These findings provide the first scientific evidence of the cytotoxicity of AME through inhibition of tubulin polymerization and HDAC8 activity through its coumarin and flavonoid content.

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      Mira, A., & Shimizu, K. (2015). In vitro Cytotoxic Activities and Molecular Mechanisms of Angelica shikokiana Extract and its Isolated Compounds. Pharmacognosy Magazine, 11(44s3), 564–569. https://doi.org/10.4103/0973-1296.172962