Abstract
Methanol extracts of the root of Dipsacus asper Wall (Dipsacaceae) were found to exhibit apoptosis-inducing activities in U937 (human monocyte-like histiocytic) cells. Investigation of the active n-BuOH fraction led to the isolation of akebia saponin D (ASD). Structure was established by spectroscopic methods. Treatment of U937 cells with ASD induced apoptosis in a dose dependent manner. ASD exerted strong cytotoxicity against human and murine leukemia cells. It is significantly increased the subG1 cell population and expression of p53 and Bax gene. And also ASD enhanced NO production from RAW264.7 macrophage cells. Taken together, these results strongly indicate that ASD may exert apoptosis-inducing activity via induction of apoptosis through activation chiefly via the nitric oxide and apoptosis-related p53 and Bax gene expression. These data provide scientific evidence that Dipsacus asper Wall can be useful as a chemopreventive agent.
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Adams, J. M. and Corry, S., The Bcl-2 protein family: Arbiters of cell survival. Science, 28, 1322–1326 (1998).
Bedir, E., Kirmizipekmez, H., Sticher, O., and Calis, I., Triterpene saponins from the fruits of Hedera helix. Phytochemistry, 53, 905–909 (2000).
Ding, A. H., Nathan, C. F., and Steuhr, D. J., Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. J. Immunol., 141, 2407–2412 (1988).
Dowdy, S. and Wearden, S., Statistics for research. Wiley, New York, p. 262 (1983).
Feng, X. Z., Dong, M., Gao, Z. J., and Xu, S. X., Three new triterpenoid saponins from Ixeris sonchifolia and their cytotoxic activity. Planta Med., 69, 1036–1040 (2003).
Fukumura, D., Kashiwagi, S., and Jain, R. K., The role of nitric oxide in tumor progression. Nat. Rev. Cancer, 6, 521–534 (2006).
Hung, T. M., Jin, W., Thuong, P. T., Song, K. S., Seong, Y. H., and Bae, K., Cytotoxic saponins from the root of Dipsacus asper Wall. Arch. Pharm. Res., 28, 1053–1056 (2005).
Jung, K. Y., Studies on the terpenoid constituents from the roots of Dipsacus asper Wall. Ph.D. Thesis, Yeungam University (1995).
Jung, K. Y., Do, J. C., and Son, K. H., Triterpene glycosides from the roots of Dipsacus asper. J. Nat. Prod., 56, 1912–1916 (1993).
Kouno, I., Tsuboi, A., Nanri, M., and Kawano, M., Acylated triterpene glycoside from roots of Dipsacus asper. Phytochemistry 29, 338–339 (1990).
McConkey, D. J., Greene, G., and Pettaway, C. A., Apoptosis resistance increases with metastatic potential in cells of the human LNCaP prostate carcinoma line. Cancer Res., 56, 5594–5599 (1996).
Miyashita, T., Krajewski, S., Krajewska, M., Wang, H. G., Lin, H. K., Liebermann, D. A., Hoffmann, B., and Reed, J. C., Tumor suppressor p53 is a regulator of Bcl-2 and bax gene expression in vitro and in vivo. Oncogene, 9, 1799–1805 (1994).
Mosmann, T., Rapid colorimetric assay for cellular growth and survival application to proliferation and cytotoxic assays. J. Immunol. Methods, 65, 55–63 (1983).
Nakadai, A., Li, Q., and Kawada, T., Chlorpyrifos induces apoptosis in human monocyte cell line U937. Toxicology 224, 202–209 (2006).
Namba, T., The encyclopedia of waken-yaku (traditional sino-japan medicines) with color pictures, vol. 1. Hoikusha Publishing, Osaka, pp. 185–186 (1993).
Ohkusu, K., Isobe, K., Hidaka, H., and Nakashima, I., Elucidation of the protein kinase C-dependent apoptosis pathway in distinct subsets of T lymphocytes in MRL-lpr/lpr mice. Eur. J. Immunol., 31, 3180–3186 (1995).
Oh, S. R., Jung, K. Y., Son, K. H., Park, S. H., Lee, I. S., Ahn, K. S., and Lee, H. K., In vitro anticomplementary activity of hederagenin saponins isolated from roots of Dipsacus asper. Arch. Pharm. Res., 22, 317–319 (1999).
Shijun, C., Jonathan, S. R., Romeo, B. M., and Jroge, J. A., Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or independent mechanisms. Cancer Res., 54, 2462–2467 (1994).
Suh, H. W., Song, D. K., Huh, S. O., Son, K. H., and Kim, Y. H., Antinociceptive mechanisms of Dipsacus saponin C administered intrathecally in mice. J. Ethnopharmacol. 71, 211–218 (2000).
Thomsen, L. L. and Miles, D. W., Role of nitric oxide in tumour progression: lessons from human tumours. Cancer Metastasis Rev. 17, 107–118 (1998).
Tsou, M. F., Lu, H. F., Chen, S. C., Wu, L. T., Chen, Y. S., Kuo, H. M., Lin, S. S., and Chung, J. G., Involvement of Bax, Bcl-2, Ca2+ and caspase-3 in capsaicin-induced apoptosis of human leukemia HL-60 cells. Anticancer Res., 26, 1965–1971 (2006).
Uramoto, H., Sugio, K., Oyama, T., Nakata, S., Ono, K., Nozoe, T., and Yasumoto, K., Expression of the p53 family in lung cancer. Anticancer Res., 26, 1785–1790 (2006).
Wang, H. B., Mayer, R., and Rcker, G., Triterpenoid glycosides from Stauntonia hexaphylla. Phytochemistry, 33, 1469–1473 (1993).
Williams, J. L., Nath, N., Chen, J., Hundley, T. R., Gao, J., Kopelovich, L., Kashfi, K., and Rigas, B., Growth inhibition of human colon cancer cells by nitric oxide (NO). Anticancer Res., 63, 7613–7618 (2003).
Yang, G. Y., Liao, J., Kim, K. H., Yurkow, E. J., and Yang, C. S., Inhibition of growth and induction of apoptosis in human cancer lines by tea polyphenols. Carcinogenesis, 19, 611–616 (1998).
Yin, C. Y., Knudson, C. M., Korsmeyer, S. J., and VanDyke, T., Bax suppresses tumorigenesis and stimulates apoptosis in vivo. Nature 385, 637–640 (1997).
Zhan, Q., Fan, S., Bae, I., Guillouf, C., Liebermann, D. A., and O’Connor, P. M., Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis. Oncogene, 9, 3743–3751 (1994).
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Jeong, SI., Zhou, B., Bae, JB. et al. Apoptosis-inducing effect of Akebia saponin D from the roots of Dipsacus asper Wall in U937 cells. Arch. Pharm. Res. 31, 1399–1404 (2008). https://doi.org/10.1007/s12272-001-2123-0
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DOI: https://doi.org/10.1007/s12272-001-2123-0