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http://dx.doi.org/10.4014/jmb.1909.09059

Kanakugiol, a Compound Isolated from Lindera erythrocarpa, Promotes Cell Death by Inducing Mitotic Catastrophe after Cell Cycle Arrest  

Lee, Jintak (Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
Chun, Hyun-Woo (Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
Pham, Thu-Huyen (Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
Yoon, Jae-Hwan (Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
Lee, Jiyon (Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
Choi, Myoung-Kwon (Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
Ryu, Hyung-Won (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
Oh, Sei-Ryang (Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology)
Oh, Jaewook (Department of Stem Cell and Regenerative Biotechnology, Konkuk University)
Yoon, Do-Young (Department of Bioscience and Biotechnology, Research Institute of Bioactive-Metabolome Network, Konkuk University)
Publication Information
Journal of Microbiology and Biotechnology / v.30, no.2, 2020 , pp. 279-286 More about this Journal
Abstract
A novel compound named 'kanakugiol' was recently isolated from Lindera erythrocarpa and showed free radical-scavenging and antifungal activities. However, the details of the anti-cancer effect of kanakugiol on breast cancer cells remain unclear. We investigated the effect of kanakugiol on the growth of MCF-7 human breast cancer cells. Kanakugiol affected cell cycle progression, and decreased cell viability in MCF-7 cells in a dose-dependent manner. It also enhanced PARP cleavage (50 kDa), whereas DNA laddering was not induced. FACS analysis with annexin V-FITC/PI staining showed necrosis induction in kanakugiol-treated cells. Caspase-9 cleavage was also induced. Expression of death receptors was not altered. However, Bcl-2 expression was suppressed, and mitochondrial membrane potential collapsed, indicating limited apoptosis induction by kanakugiol. Immunofluorescence analysis using α-tubulin staining revealed mitotic exit without cytokinesis (4N cells with two nuclei) due to kanakugiol treatment, suggesting that mitotic catastrophe may have been induced via microtubule destabilization. Furthermore, cell cycle analysis results also indicated mitotic catastrophe after cell cycle arrest in MCF-7 cells due to kanakugiol treatment. These findings suggest that kanakugiol inhibits cell proliferation and promotes cell death by inducing mitotic catastrophe after cell cycle arrest. Thus, kanakugiol shows potential for use as a drug in the treatment of human breast cancer.
Keywords
Kanakugiol; breast cancer; necrosis; mitotic catastrophe; cell cycle arrest;
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