Abstract
Paris polyphylla Smith var. yunnanensis extracts, Rhizoma Paridis saponins (RPS) have been found to show strong antitumor activity. However, few studies have yet investigated pulmonary metastasis treatment with this herb. To detail the effective components in RPS and discuss the preliminary mechanism of antitumor effects in vivo and in vitro, a mixture isolated from RPS was investigated. The main constituents were identified as polyphyllin D, formosanin C, dioscin, Paris H, Paris VII and pennogennin 3-O-α-L-rhamnopyranosyl (1→4)-[β-L-rhamnopyranosyl (1→2)]-β-D-glucopyranoside. In our experiments, LA795 cells were exposed to the mixed compounds. Migration inhibition was evaluated by wound healing assay and migration assay in non-cytotoxic dose which was determined by MTT assay. The results demonstrated that the constituent in varying degrees inhibited the migration of the tumor cells in vitro. The mixture also showed antitumor effects on carcinoma in vivo. In conclusion, the mixture is a potent anticancer agent that elicits programmed cell death and inhibits the migration in murine lung adenocarcinoma, both in vitro and in vivo.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Reference
Cai, J., Liu, M., Wang, Z., and Ju, Y., Apoptosis induced by dioscin in Hela cells. Biol. Pharm. Bull., 25, 193–196 (2002).
Cheung, J. Y., Ong, R. C., Suen, Y. K., Ooi, V., Wong, H. N., Mak, T. C., Fung, K. P., Yu, B., and Kong, S. K., Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells. Cancer Lett., 217, 203–211 (2005).
Jang, A. and Hill, R. P., Drug sensitivity and metastatic ability in B16 melanoma cells. Clin. Exp. Metastasis, 9, 393–402 (1991).
Ji, S., Zhou, T. S., and Chang, C. Z., Determination of Antitumor cytotoxic active substance gracillin in Rhizoma Paridis and yunnan white. Chinese Traditional Patent Medicine, 23, 212–215 (2001).
Jiang, J. G., Ning, Y. G., Chen, C., Ma, D., Liu, Z. J., Yang, S., Zhou, J., Xiao, X., Zhang, X. A., Edin, M. L., Card, J. W., Wang, J., Zeldin, D. C., and Wang, D. W., Cytochrome p450 epoxygenase promotes human cancer metastasis. Cancer Res., 67, 6665–6674 (2007).
Lee, M. S., Yuet-Wa, J. C., Kong, S. K., Yu, B., Eng-Choon, V. O., Nai-Ching, H. W., Chung-Wai, T. M., and Fung, K. P., Effects of polyphyllin D, a steroidal saponin in Paris polyphylla, in growth inhibition of human breast cancer cells and in xenograft. Cancer Biol. Ther., 4, 1248–1254 (2005).
Liu, M. J., Wang, Z., Ju, Y., Zhou, J. B., Wang, Y., and Wong, R. N., The mitotic-arresting and apoptosis-inducing effects of diosgenyl saponins on human leukemia cell lines. Biol. Pharm. Bull., 27, 1059–1065 (2004).
Man, S., Zhang, Y., Gao, W., Yan, L., and Ma, C., Cyclophosphamide promotes pulmonary metastasis on mouse lung adenocarcinoma. Clin. Exp. Metastasis, 25, 855–864 (2008).
Man, S., Gao, W., Zhang, Y., Yan, L., Ma, C., Liu, C., and Huang, L., Antitumor and antimetastatic activities of Rhizoma Paridis saponins. Steroids, 74, 1051–1056 (2009).
Nam, D. H., Jeon, H. M., Kim, S., Kim, M. H., Lee, Y. J., Lee, M. S., Kim, H., Joo, K. M., Lee, D. S., Price, J. E., Bang, S. I., and Park, W. Y., Activation of notch signaling in a xenograft model of brain metastasis. Clin. Cancer Res., 14, 4059–4066 (2008).
Nguyen, V. T., Darbour, N., Bayet, C., Doreau, A., Raad, I., Phung, B. H., Dumontet, C., Di Pietro, A., Dijoux-Franca, M. G., and Guilet, D., Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla. Fitoterapia, 80, 39–42 (2009).
Ong, R. C., Lei, J., Lee, R. K., Cheung, J. Y., Fung, K. P., Lin, C., Ho, H. P., Yu, B., Li, M., and Kong, S. K., Polyphyllin D induces mitochondrial fragmentation and acts directly on the mitochondria to induce apoptosis in drug-resistant HepG2 cells. Cancer Lett., 261, 158–164 (2008).
Ravikumar, P. R., Hammesfahr, P., and Sih, C. J., Cytotoxic saponins from the Chinese herbal drug Yunnan Bai Yao. J. Pharm. Sci., 68, 900–903 (1979).
Singh, A. V., Xiao, D., Lew, K. L., Dhir, R., and Singh, S. V., Sulforaphane induces caspase-mediated apoptosis in cultured PC-3 human prostate cancer cells and retards growth of PC-3 xenografts in vivo. Carcinogenesis, 25, 83–90 (2004).
Siu, F. M., Ma, D. L., Cheung, Y. W., Lok, C. N., Yan, K., Yang, Z., Yang, M., Xu, S., Ko, B. C., He, Q. Y., and Che, C. M., Proteomic and transcriptomic study on the action of a cytotoxic saponin (Polyphyllin D): induction of endoplasmic reticulum stress and mitochondria-mediated apoptotic pathways. Proteomics, 8, 3105–3117 (2008).
Struyf, S., Burdick, M. D., Peeters, E., Van den Broeck, K., Dillen, C., Proost, P., Van Damme, J., and Strieter, R. M., Platelet factor-4 variant chemokine CXCL4L1 inhibits melanoma and lung carcinoma growth and metastasis by preventing angiogenesis. Cancer Res., 67, 5940–5948 (2007).
Wang, T., Liu, Z., Li, J., Zhong, M., Li, J., Chen, X., and Bi, K., Determination of protodioscin in rat plasma by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 848, 363–368 (2007a).
Wang, Y., Cheung, Y. H., Yang, Z., Chiu, J. F., Che, C. M., and He, Q. Y., Proteomic approach to study the cytotoxicity of dioscin (saponin). Proteomics, 6, 2422–2432 (2006).
Wang, Y., Zhang, Y. J., Gao, W. Y., and Yan, L. L., Anti-tumor constituents from Paris polyphylla var. yunnanensis. Zhongguo Zhong Yao Za Zhi, 32, 1425–1428 (2007b).
Wang, Y., Gao, W. Y., Zhang, T. J., and Guo, Y. Q., A novel phenylpropanoid glycosides and a new derivation of phenolic glycoside from Paris Polyphylla var. yunnanensis. Chinese Chem. Lett., 18, 548–550 (2007c).
Wu, R. T., Chiang, H. C., Fu, W. C., Chien, K. Y., Chung, Y. M., and Horng, L. Y., Formosanin-C, an immunomodulator with antitumor activity. Int. J. Immunopharmacol., 12, 777–786 (1990).
Wu, S.-S., Gao, W.-Y., Duan, H.-Q., and Jia, W., Advances in studies on chemical constituents and pharmacological activities of Rhizoma Paridis. Chinese Traditional and Herbal Drugs, 35, 344–347 (2004).
Xiao, X., Bai, P., Bui Nguyen, T. M., Xiao, J., Liu, S., Yang, G., Hu, L., Chen, X., Zhang, X., Liu, J., and Wang, H., The antitumoral effect of Paris Saponin I associated with the induction of apoptosis through the mitochondrial pathway. Mol. Cancer Ther., 8, 1179 (2009).
Yan, L., Gao, W., Zhang, Y., and Wang, Y., A new phenylpropanoid glycosides from Paris polyphylla var. yunnanensis. Fitoterapia, 79, 306–307 (2008).
Yan, L. L., Zhang, Y. J., Gao, W. Y., Man, S. L., and Wang, Y., In vitro and in vivo anticancer activity of steroid saponins of Paris polyphylla var. yunnanensis. Exp. Oncol., 31, 27–32 (2009).
Yun, H., Li, J. C., Wen, H. Z., Yu, H. D., Yong, L. W., Qiang, W., and Ding, Z., Separation and identification of steroidal compounds with cytotoxic activity against human gastric cancer cell lines in vitro from the rhizomes of Paris polyphylla var. chinensis. Chem. Nat. Compd., 43, 672–677 (2007).
Zhang, S.-P., Research progression chemical constituents and pharmacological effect of Genus paris. Strait Pharmaceutical Journal, 19, 4–7 (2007).
Zhang, Y., Li, H. Z., Zhang, Y. J., Jacob, M. R., Khan, S. I., Li, X. C., and Yang, C. R., Atropurosides A-G, new steroidal saponins from Smilacina atropurpurea. Steroids, 71, 712–719 (2006).
Author information
Authors and Affiliations
Corresponding author
Additional information
These two authors contributed equally to this work.
Rights and permissions
About this article
Cite this article
Shuli, M., Wenyuan, G., Yanjun, Z. et al. Paridis saponins inhibiting carcinoma growth and metastasis In vitro and in vivo . Arch. Pharm. Res. 34, 43–50 (2011). https://doi.org/10.1007/s12272-011-0105-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-011-0105-4