G1 phase arrest of the cell cycle by a ginseng metabolite, compound K, in U937 human monocytic leukamia cells
We recently reported that the ginseng saponin metabolite, compound K (20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol, IH901), inhibits the growth of U937 cells through caspase-dependent apoptosis pathway. In this study, we further characterized the effects of compound K on U937 cells and found that, in addition to apoptosis, compound K induced the arrest of the G1 phase. The compound K treated U937 cells showed increased p21 expression; an inhibitory protein of cyclin-cdk complex. The up-regulation of p21 was followed by the inactivation of cyclin D and the cdk4 protein, which act at the early G1 phase, and cyclin E, which acts at the late G1 phase. Furthermore, compound K induced the activation of JNK and the transcription factor AP-1, which is a downstream target of JNK. These findings suggest that the up-regulation of p21 and activation of JNK in the compound K treated cells contribute to the arrest of the G1 phase.
Key wordsCompound K U937 cell Apoptosis G1 phase p21 AP-1 JNK
Unable to display preview. Download preview PDF.
- Bunnett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sasata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., Bhagwat, S. S., Manning, A. M., and Anderson, D. W., SP600125, an anthrapyrazolone inhibitor of JunN-terminal kinase.Proc. Natl. Acad. Sci. U.S.A., 98, 13681–13686 (2001).CrossRefGoogle Scholar
- Hasegawa, H., Matsumiya, S., Uchiyama, M., Kurokawa, T., Inouye, Y., Kasai, R., Ishibashi, S., and Yamasaki, K., Inhibitory effect of some triterpenoid saponins on glucose transport in tumor cells and its application toin vitro cytotoxic and antiviral activities.Planta. Med., 60, 240–243 (1995).CrossRefGoogle Scholar
- Kang, K., Lim, H. K., Kim, S. U., Kim, Y. W., Kim, W. T., Chung, H. S., Choo, M. K., Kim, D. H., Kim, H. S., Shim, M. J., Chung, M. H., and Hyun, J. W., Induction of apoptosis by ginseng saponin metabolite in U937 human monocytic leukemia cells.J. Food Biochem., 29, 29–40 (2005).CrossRefGoogle Scholar
- Kim, H. S., Seo, H., Yang, C., and Kim, K. S., Noradrenergicspecific transcription of the dopamine β-hydroxylase gene requires synergy of multiplecis-acting elements including at least two phox-2a binding sites.J. Neuroscience, 18, 8247–8260 (1998).Google Scholar
- Slebos, R. J. C., Lee, M. H., Plunkett, B. S., Kessis, T. D., Williams, B. O., Jacks, T., Hedrick, L., Kastan, M. B., and Cho, K. R., p53 dependent G1 arrest involves pRB related proteins and is disrupted by the human papillomavirus 16 E7 oncoprotein.Proc. Natl. Acad. Sci. U.S.A., 91, 5320–5324. (1994).PubMedCrossRefGoogle Scholar
- Zada, A. A., Singh, S. M., Reddy, V. A., Elsasser, A., Meisel, A., Haferlach, T., Tenen, D. G., Hiddemann, W., and Behre, G., Downregulation of c-Jun expression and cell cycle regulatory molecules in acute myeloid leukemia cells upon CD44 ligation.Oncogene, 22, 2296–2308 (2003).PubMedCrossRefGoogle Scholar