Abstract
Cytotoxicity-guided fractionation and separation of MeOH extract from Androsace umbellata (Lour.) Merr. led to the isolation of four triterpenoid saponins. Compounds isolated from the n-BuOH soluble fraction were identified as saxifragifolin C (1), A (2), B (3), and D (4) by spectroscopic analysis. Antiproliferative effect of isolated compounds were evaluated by the sulforhodamin B assay against multidrug resistance (MDR; MES-SA/DX5 and HCT15/CLO2) and non-MDR (A549, SK-OV-3, SK-MEL-2, MES-SA, and HCT15) human tumor cell lines. All compounds exhibited strong cytotoxicity against non-MDR human tumor cell lines with IC50 values of 0.19–2.37 μM. MDR cells and non-MDR cells had similar sensitivity to these compounds, however, MDR cells were highly resistant to doxorubicin. Compounds 1–4 induced an increase in the percentage of Annexin V-binding cells, indicating that 1–4 induced apoptosis in RAW 264.7 cells. Also, the condensation of nuclei, a characteristic morphological change of apoptosis, was observed in RAW 264.7 cells by the treatment with n-BuOH fraction, compounds 3 and 4, respectively.
Similar content being viewed by others
References
Araki, T., Yamamoto, A., and Yamada, M., Accurate determination of DNA content in single cell nuclei stained with Hoechst 33258 fluorochrome at high salt concentration. Histochemistry, 87, 331–338 (1987).
Bloor, S. J. and Qi, L., Cytotoxic saponins from new zealand Myrsine species. J. Nat. Prod., 57, 1354–1360 (1994).
Choi, S. U., Kim, N. Y., Choi, E. J., Kim, K. H., and Lee, C. O., Establishment of doxorubicin-resistant subline derived from HCT15 human colorectal cancer cells. Arch. Pharm. Res., 19, 342–347 (1996).
Endicott, J. A. and Ling, V., The biochemistry of p-glycoproteinmediated multidrug resistance. Annu. Rev. Biochem., 58, 137–171 (1989).
Jia, Z., Koike, K., Ohmoto, T., and Ni, M., Triterpenoid saponins from Ardisia crenata. Phytochemistry, 37, 1389–1396 (1994).
Lee, T. B., Coloured flora of Korea(2). Hyangmoonsa, Seoul, pp. 41, (2003).
Lee, W. T., Coloured standard illustrations of Korea plants. Academybook, Seoul, pp. 270, (1996).
Li, C. H., Yin, Z. Q., Huang, X. J., Wang, L., and Ye, W. C., Chemical constituents from Androsace umbellata. Zhongguo Tianran Yaowu, 6, 123–125 (2008).
Liu, X., Shibata, T., Hisaka, S., Kawai, Y., and Osawa, T., DHA Hydroperoxides as a potential inducer of neuronal cell death: A mitochondrial dysfunction-mediated pathway. J. Clin. Biochem. Nutr., 43, 26–33 (2008).
Pal, B. C. and Mahato, S. B., New triterpenoid pentasaccharides from Androsace saxifragifolia. J. Chem. Soc. Perkin Trans. I, 9, 1963–1967 (1987).
Skehan, P., Storeng, R., Scudiero, D., Monks, A., Mcmahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 82, 1107–1112 (1990).
Teodori, E., Dei, S., Scapecchi, S., and Gualtieri, F., The medicinal chemistry of multidrug resistance (MDR) reversing drugs. Farmaco, 57, 385–415 (2002).
Waltho, J. P., Williams, D. H., Mahato, S. B., Pal, B. C., and Barna, J. C. J., Structure elucidation of two triterpenoid tetrasaccharides from Androsace saxifragifolia. J. Chem. Soc. Perkin Trans. I, 8, 1527–1531 (1986).
Wang, Y., Zhang, D., Ye, W., Yin, Z., Fung, K. P., Zhao, S., and Yao, X., Triterpenoid saponins from Androsace umbellata and their anti-proliferative activities in human hepatoma cells. Planta Med., 74, 1280–1284 (2008).
Yao, G., Yang, L., Hu, Y., Liang, J., Liang, J., and Hou, Y., Nonylphenol-induced thymocyte apoptosis involved caspase-3 activation and mitochondrial depolarization. Mol. Immunol., 43, 915–926 (2006).
Zhang, D. M., Wang, Y., Tang, M. K., Chan, Y. W., Lam, H. M., Ye, W. C., and Fung, K. P., Saxifragifolin B from Androsace umbellata induced apoptosis on human hepatoma cells. Biochem. Biophys. Res. Commun., 362, 759–765 (2007).
Zhonghuabencao Compilation Committee, Zhonghuabencao (6). Shanghai Science and Technologic Publisher, pp. 87–89, (1999).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Park, J.H., Kwak, J.H., Khoo, J.H. et al. Cytotoxic effects of triterpenoid saponins from Androsace umbellata against multidrug resistance (MDR) and non-MDR cells. Arch. Pharm. Res. 33, 1175–1180 (2010). https://doi.org/10.1007/s12272-010-0807-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-010-0807-z