DOI QR코드

DOI QR Code

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)
  • Received : 2019.09.30
  • Accepted : 2019.12.14
  • Published : 2020.02.28

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

References

  1. Phosri S, Jangpromma N, Chang LC, Tan GT, Wongwiwatthananukit S, Maijaroen S, et al. 2018. Siamese crocodile white blood cell extract inhibits cell proliferation and promotes autophagy in multiple cancer cell lines. J. Microbiol. Biotechnol. 28: 1007-1021. https://doi.org/10.4014/jmb.1712.12002
  2. Holland AJ, Cleveland DW. 2012. Losing balance: the origin and impact of aneuploidy in cancer. EMBO Rep. 13: 501-514. https://doi.org/10.1038/embor.2012.55
  3. Gordon DJ, Resio B, Pellman D. 2012. Causes and consequences of aneuploidy in cancer. Nat. Rev. Genet. 13: 189-203. https://doi.org/10.1038/nrg3123
  4. Boveri T. 2008. Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. J. Cell Sci. 121 Suppl 1: 1-84. https://doi.org/10.1242/jcs.025742
  5. Yoon JH, Pham TH, Lee J, Lee J, Ryu HW, Oh SR, et al. 2019. Methyl linderone suppresses TPA-stimulated IL-8 and MMP-9 expression via the ERK/STAT3 pathway in MCF-7 breast cancer cells. J. Microbiol. Biotechnol. 10.4014/jmb.1911.11068.
  6. Jones EF, Ray KM, Li W, Seo Y, Franc BL, Chien AJ, et al. 2017. Dedicated breast positron emission tomography for the evaluation of early response to neoadjuvant chemotherapy in breast cancer. Clin. Breast Cancer 17: e155-e159. https://doi.org/10.1016/j.clbc.2016.12.008
  7. Howell A, Anderson AS, Clarke RB, Duffy SW, Evans DG, Garcia-Closas M, et al. 2014. Risk determination and prevention of breast cancer. Breast Cancer Res. 16: 446. https://doi.org/10.1186/s13058-014-0446-2
  8. Gewirtz DA. 2000. Growth arrest and cell death in the breast tumor cell in response to ionizing radiation and chemotherapeutic agents which induce DNA damage. Breast Cancer Res. Treat. 62: 223-235. https://doi.org/10.1023/A:1006414422919
  9. Morse DL, Gray H, Payne CM, Gillies RJ. 2005. Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells. Mol. Cancer Ther. 4: 1495-1504. https://doi.org/10.1158/1535-7163.MCT-05-0130
  10. Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, et al. 2015. Broad targeting of resistance to apoptosis in cancer. Semin. Cancer Biol. 35 Suppl: S78-S103. https://doi.org/10.1016/j.semcancer.2015.03.001
  11. Dumontet C, Jordan MA. 2010. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat. Rev. Drug Discov. 9: 790-803. https://doi.org/10.1038/nrd3253
  12. Vitale I, Galluzzi L, Castedo M, Kroemer G. 2011. Mitotic catastrophe: a mechanism for avoiding genomic instability. Nat. Rev. Mol. Cell Biol. 12: 385-392. https://doi.org/10.1038/nrm3115
  13. Ali AG, Mohamed MF, Abdelhamid AO, Mohamed MS. 2017. A novel adamantane thiadiazole derivative induces mitochondria-mediated apoptosis in lung carcinoma cell line. Bioorg. Med. Chem. 25: 241-253. https://doi.org/10.1016/j.bmc.2016.10.040
  14. Moubarak RS, Yuste VJ, Artus C, Bouharrour A, Greer PA, Menissier-de Murcia J, et al. 2007. Sequential activation of poly(ADP-ribose) polymerase 1, calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis. Mol. Cell Biol. 27: 4844-4862. https://doi.org/10.1128/MCB.02141-06
  15. Nicotera P, Lipton SA. 1999. Excitotoxins in neuronal apoptosis and necrosis. J. Cereb. Blood Flow Metab. 19: 583-591. https://doi.org/10.1097/00004647-199906000-00001
  16. Shah GM, Shah RG, Poirier GG. 1996. Different cleavage pattern for poly(ADP-ribose) polymerase during necrosis and apoptosis in HL-60 cells. Biochem. Biophys. Res. Commun. 229: 838-844. https://doi.org/10.1006/bbrc.1996.1889
  17. Mc Gee MM. 2015. Targeting the mitotic catastrophe signaling pathway in cancer. Mediators Inflamm. 2015: 146282. https://doi.org/10.1155/2015/146282
  18. Galluzzi L, Vitale I, Abrams JM, Alnemri ES, Baehrecke EH, Blagosklonny MV, et al. 2012. Molecular definitions of cell death subroutines: recommendations of the nomenclature committee on cell death 2012. Cell Death Differ. 19: 107-120. https://doi.org/10.1038/cdd.2011.96
  19. Fan H, Zheng T, Chen Y, Yang GZ. 2012. Chemical constituents with free-radical-scavenging activities from the stem of Fissistigma polyanthum. Pharmacogn. Mag. 8: 98-102. https://doi.org/10.4103/0973-1296.96549
  20. Hwang EI, Lee YM, Lee SM, Yeo WH, Moon JS, Kang TH, et al. 2007. Inhibition of chitin synthase 2 and antifungal activity of lignans from the stem bark of Lindera erythrocarpa. Planta Med. 73: 679-682. https://doi.org/10.1055/s-2007-981526
  21. Zhao YR, L i HM, Zhu M, L i J, Ma T, Huo Q , et al. 2018. Non-benzoquinone geldanamycin analog, WK-88-1, induces apoptosis in human breast cancer cell lines. J. Microbiol. Biotechnol. 28: 542-550. https://doi.org/10.4014/jmb.1710.10063
  22. Marino G, Kroemer G. 2013. Mechanisms of apoptotic phosphatidylserine exposure. Cell Res. 23: 1247-1248. https://doi.org/10.1038/cr.2013.115
  23. Tacar O, Sriamornsak P, Dass CR. 2013. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J. Pharm. Pharmacol. 65: 157-170. https://doi.org/10.1111/j.2042-7158.2012.01567.x
  24. Majtnerova P, Rousar T. 2018. An overview of apoptosis assays detecting DNA fragmentation. Mol. Biol. Rep. 45: 1469-1478. https://doi.org/10.1007/s11033-018-4258-9
  25. Fulda S, Debatin KM. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25: 4798-4811. https://doi.org/10.1038/sj.onc.1209608
  26. Siddiqui WA, Ahad A, Ahsan H. 2015. The mystery of BCL2 family: Bcl-2 proteins and apoptosis: an update. Arch. Toxicol. 89: 289-317. https://doi.org/10.1007/s00204-014-1448-7
  27. Taylor RC, Cullen SP, Martin SJ. 2008. Apoptosis: controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 9: 231-241. https://doi.org/10.1038/nrm2312
  28. Thakur B, Kumar Y, Bhatia A. 2019. Programmed necrosis and its role in management of breast cancer. Pathol. Res. Pract. 215: 152652. https://doi.org/10.1016/j.prp.2019.152652
  29. Pucci B, Kasten M, Giordano A. 2000. Cell cycle and apoptosis. Neoplasia 2: 291-299. https://doi.org/10.1038/sj/neo/7900101
  30. Riccardi C, Nicoletti I. 2006. Analysis of apoptosis by propidium iodide staining and flow cytometry. Nat. Protoc. 1: 1458-1461. https://doi.org/10.1038/nprot.2006.238