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9-Oxo-(10E,12E)-octadecadienoic acid, a cytotoxic fatty acid ketodiene isolated from eggplant calyx, induces apoptosis in human ovarian cancer (HRA) cells

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Abstract

9-Oxo-(10E,12E)-octadecadienoic acid (9-EE-KODE), which is isolated from the calyx of eggplants, exhibits cytotoxic activity against human ovarian cancer (HRA) cells. The aim of the present study is to clarify the action mechanism of 9-EE-KODE leading to cell death. After the treatment of 9-EE-KODE in HRA cells, we found intracellular DNA fragmentation, surface-exposure of phosphatidylserine in the outer cell membrane, and increased caspase-3/7 activities in the HRA cells. The dissipation of mitochondrial membrane potential, release of cytochrome c from mitochondria to cytosol, down-regulation of Bcl-2, and up-regulation of Bax levels were also found in 9-EE-KODE-treated cells in a dose-dependent manner. These results demonstrated that 9-EE-KODE induced apoptosis in HRA cells via the mitochondrial regulation pathway.

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Acknowledgments

The authors are grateful to Prof. Tsunehiko Higuchi and Dr. Nobuki Kato, Graduate School of Pharmaceutical Sciences, Nagoya City University for supporting the synthesis of 9-EE-KODE. We also thank Dr. Kiyosumi Shibata, Graduate School of Medicine, Nagoya University for providing us with the HRA cell line.

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Author notes

  1. Hajime Mizukami

    Present address: The Kochi Prefectural Makino Botanical Garden, 4200-6 Godaisan, Kochi, 781-8125, Japan

Authors and Affiliations

  1. Department of Pharmacognosy, Graduate School of Pharmaceutical Science, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, 467-8603, Japan

    Baiyang Zhao, Hajime Mizukami & Toshiaki Makino

  2. Tomoda Clinic, 30-1 Akechiyama, Shinmaiko, Chita, 478-0036, Japan

    Yutaka Tomoda

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  1. Baiyang Zhao
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  2. Yutaka Tomoda
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  3. Hajime Mizukami
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  4. Toshiaki Makino
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Correspondence to Toshiaki Makino.

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Zhao, B., Tomoda, Y., Mizukami, H. et al. 9-Oxo-(10E,12E)-octadecadienoic acid, a cytotoxic fatty acid ketodiene isolated from eggplant calyx, induces apoptosis in human ovarian cancer (HRA) cells. J Nat Med 69, 296–302 (2015). https://doi.org/10.1007/s11418-015-0892-x

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  • DOI: https://doi.org/10.1007/s11418-015-0892-x

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