Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis

  • Authors:
    • Hideaki Kawakita
    • Akihiko Tsuchida
    • Keisuke Miyazawa
    • Munekazu Naito
    • Masatoshi Shigoka
    • Bunso Kyo
    • Masanobu Enomoto
    • Tatehiko Wada
    • Kenji Katsumata
    • Kazuma Ohyashiki
    • Masahiro Itoh
    • Akio Tomoda
    • Tatsuya Aoki
  • View Affiliations

  • Published online on: June 1, 2009     https://doi.org/10.3892/ijmm_00000184
  • Pages: 709-716
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Abstract

Vitamin K2 (menaquinone-4: MK4) has been reported to inhibit cell growth and induce apoptosis in various tumor cells. We examined the effects of MK4 using three types of colon cancer cell lines: PMCO1, COLO201, and DLD-1. Exposure to MK4 was at concentrations from 5 to 50 µM, growth inhibitory effects were observed dose-dependently in COLO201 and PMCO1, whereas the growth inhibition observed in DLD-1 was minimal. Comparison of COLO201 and PMCO1 cells exhibiting distinct growth inhibitory effects showed that cell death via apoptosis accompanied by activation of caspase-3 was induced in PMCO1, while apoptosis was not induced in COLO201. On the contrary, immunoblot assay using an anti-LC3B antibody showed autophagy induction by addition of MK4 and incubation in all three types of colon cancer cell lines. Addition of 3-methyladenine (3-MA) attenuated the growth inhibitory effect of MK4 in COLO201, whereas no influence of 3-MA was noted in PCMO1. Electron microscopy images of COLO201 showed that addition of MK4 induced an increased number of cytoplasmic autophagosomes and autolysosomes as well as morphological changes including scantiness of cytoplasm accompanied by loss of cell organelles, nuclear shrinkage, and fragmentation of cytoplasmic membrane in some cells, indicating the induction of cell death via autophagy not accompanied by the formation of apoptotic bodies in COLO201 cells. These results suggested that the response to MK4 and the way of induction of cell death vary in different colon cancer cell lines.

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June 2009
Volume 23 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kawakita H, Tsuchida A, Miyazawa K, Naito M, Shigoka M, Kyo B, Enomoto M, Wada T, Katsumata K, Ohyashiki K, Ohyashiki K, et al: Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis . Int J Mol Med 23: 709-716, 2009
APA
Kawakita, H., Tsuchida, A., Miyazawa, K., Naito, M., Shigoka, M., Kyo, B. ... Aoki, T. (2009). Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis . International Journal of Molecular Medicine, 23, 709-716. https://doi.org/10.3892/ijmm_00000184
MLA
Kawakita, H., Tsuchida, A., Miyazawa, K., Naito, M., Shigoka, M., Kyo, B., Enomoto, M., Wada, T., Katsumata, K., Ohyashiki, K., Itoh, M., Tomoda, A., Aoki, T."Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis ". International Journal of Molecular Medicine 23.6 (2009): 709-716.
Chicago
Kawakita, H., Tsuchida, A., Miyazawa, K., Naito, M., Shigoka, M., Kyo, B., Enomoto, M., Wada, T., Katsumata, K., Ohyashiki, K., Itoh, M., Tomoda, A., Aoki, T."Growth inhibitory effects of vitamin K2 on colon cancer cell lines via different types of cell death including autophagy and apoptosis ". International Journal of Molecular Medicine 23, no. 6 (2009): 709-716. https://doi.org/10.3892/ijmm_00000184