Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Inhibition of Phospholipase $C{\Upsilon}1$ and Cancer Cell Proliferation by Lignans and Flavans from Machilus thunbergii

  • Lee, Ji-Suk (Research group of Pain and Neuroscience, East-West Medical Research Institute, Kyoung Hee University, College of Pharmacy and Research Institute to Pharmaceutical Sciences, Seoul National University) ;
  • Kim, Jin-Woong (College of Pharmacy and Research Institute to Pharmaceutical Sciences, Seoul National University) ;
  • Yu, Young-Uck (College of Pharmacy and Research Institute to Pharmaceutical Sciences, Seoul National University) ;
  • Kim , Young-Choong (College of Pharmacy and Research Institute to Pharmaceutical Sciences, Seoul National University)
  • Published : 2004.01.01
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Abstract

Thirteen compounds were isolated from the $CH_2Cl_2$ fraction of Machilus thunbergii as phospholipase $C{\Upsilon}1\;(PLC{\Upsilon}1)$ inhibitors. These compounds were identified as nine lignans, two neolignans, and two flavans by spectroscopic analysis. Of these, 5,7-di-O-methyl-3',4'-methylenated (-)-epicatechin (12) and 5,7,3'-tri-O-methyl (-)-epicatechin (13) have not been reported previously in this plant. In addition, seven compounds, machilin A (1), (-)-sesamin (3), machilin G (5), (+)-galbacin (9), licarin A (10), (-)-acuminatin (11) and compound 12 showed dose-dependent potent inhibitory activities against $PLC{\Upsilon}1$ in vitro with $IC_{50}$ values ranging from 8.8 to 26.0 ${\mu}M$. These lignans, neolignans, and flavans are presented as a new class of $PLC{\Upsilon}1$ inhibitors. The brief study of the structure activity relationship of these compounds suggested that the benzene ring with the methylene dioxy group is responsible for the expression of inhibitory activities against $PLC{\Upsilon}1$. Moreover, it is suggested that inhibition of $PLC{\Upsilon}1$ may be an important mechanism for an antiproliferative effect on the human cancer cells. Therefore, these inhibitors may be utilized as cancer chemotherapeutic and chemopreventive agents.

Keywords

References

  1. Achenbach, H., Grob, J., Dominguez, X. A., Cano, G., Star, J. V., Brussolo, L. D. C., Munoz, G., Salgad, F., and Lopez, L., Lignans, neolignans, and norneolignans from Krameria cystisoides. Phytochemstry, 26, 1159-1166 (1987) https://doi.org/10.1016/S0031-9422(00)82370-5
  2. Ajaneyulu, A. S. R., Rao, A. M., Rao, V. K., Row, L. R., Pelter, A., and Ward, R. S., Novel hydroxy lignans from the heartwood of Gmelina arborea. Tetrahedron, 33, 133-143 (1977) https://doi.org/10.1016/0040-4020(77)80444-4
  3. Arteaga, C. L., Johnson, M. D., Todderud, G., Coffey, R. J., Carpenter, G., and Page, D. L., Elevated content of the tyrosine kinase substrate phospholipase C-gamma 1 in primary human breast carcinomas. Proc. Natl. Acad. Sci. U.S.A.,88, 10435-10439 (1991) https://doi.org/10.1073/pnas.88.23.10435
  4. Berridge, M. J., Inositol triphosphate and calcium signaling. Nature, 361,315-325 (1993) https://doi.org/10.1038/361315a0
  5. EI-Feraly, F. S., Cheatham, S. F., Hufford, C. D., and Li, W. S., Optical resolution of (${\pm}$)-dehydrodiisoeugenol: structure revision of acuminatin. Phytochemistry, 21, 1133-1135(1982) https://doi.org/10.1016/S0031-9422(00)82431-0
  6. Hill, S. R., Bonjouklian, R., Powis, G., Abraham, R. T., Ashendel, C. L., and Zalkow, L. H., A multisarnple assay for inhibitors of phosphatidylinositol phospholipase C: identification of naturally occurring peptide inhibitors with antiproliferative activity. Anti-Cancer Drug Design, 9, 353-361 (1994)
  7. Holloway, D. and Scheinmann, F., Two lignans from Litsea grandis and L. gracilipes. Phytochemistry, 13, 1233-1236 (1974) https://doi.org/10.1016/0031-9422(74)80107-X
  8. Kim, J. K., Illustrated Natural Drugs Encyclopedia, Namsandang, Seoul, Vol. 2. p. 48 (1984).
  9. King, F. E. and Wilson, J. G., The chemistry of extractives from hardwoods. Part XXXVI. The Iignans of Guaiacum officinale L. J. Chem. Soc., 4011-4024 (1964) https://doi.org/10.1039/jr9640004011
  10. Lee, J. S., Park, S. Y, Kim, J. Y, Oh, W. K., Lee, H. S., Ahn, J. S., and Kim, J., Isolation of phospholipase C$\gamma$1 inhibitors from Anemarrhena asphodeloides. Seoul Natl. Univ. J. Pharm. Sci, 21, 30-42 (1996a)
  11. Lee, H. S., Oh, W. K., Kim, B. Y, Ahn, S. C., Kang, D.O., Shin, D. I., Kim, J., Mheen, T. I., and Ahn, J. S., Inhibition of phospholipase C$\gamma$1 activity by amentoflavone isolated from Selaginella tamariscina. Planta Med., 62, 293-296 (1996b) https://doi.org/10.1055/s-2006-957887
  12. Lee, J. S., Cho, Y S., Park, E. J., Kim, J., Oh, W. K., Lee, H. S., and Ahn, J. S., Phospholipase C$\gamma$1 inhibitory principles from the sarcotestas of Ginkgo biloba. J. Nat. Prod., 61,867-872 (1998) https://doi.org/10.1021/np970367q
  13. Lee, J. S., Cho, Y S., Kim, J., Lee, H. S., and Ahn, J. S., Phospholipase C$\gamma$1 inhibitory principles from the sarcotestas of Ginkgo biloba (2). Kor. J. Pharmacogn., 30, 280-283 (1999a)
  14. Lee, J. S., Yang, M. Y, Yeo, H., Kim, J., Lee, H. S., and Ahn, J. S., Uncarinic acids, phospholipase C$\gamma$1 inhibitors from hooks of Uncaria rhynchophylla. Bioorg. Med. Chem. Lett., 9, 1429-1432 (1999b) https://doi.org/10.1016/S0960-894X(99)00211-5
  15. Lee, J. S., Kim, J., Kim, B. Y, Lee, H. S., and Ahn, J. S., Inhibition of phospholipase C$\gamma$1 and cancer cell proliferation by triterpene esters from Uncaria rhynchophylla. J. Nat. Prod., 63, 753-756 (2000) https://doi.org/10.1021/np990478k
  16. Lee, J. S. and Kim, J., Phospholipase C$\gamma$ as a target for the development of new anticancer agents from natural sources. Drugs Future, 26,163-173 (2001) https://doi.org/10.1358/dof.2001.026.02.858704
  17. Miyamura, M., Nohara, T., Tomimatsu, T., and Nishioka, I., Seven aromatic compounds from bark of Cinnamomum cassia. Phytochemistry, 22, 215-218 (1983) https://doi.org/10.1016/S0031-9422(00)80092-8
  18. Nishizuka, Y, Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science, 258, 607-614 (1992) https://doi.org/10.1126/science.1411571
  19. Noh, D. Y., Lee, Y. H., Kim, S. S., Kim, Y. I., Ryu, S. H., SUh, P. G., and Park, J. G., Elevated content of phospholipase C$\gamma$1 in colorectal cancer tissues. Cancer, 73, 36-41 (1994) https://doi.org/10.1002/1097-0142(19940101)73:1<36::AID-CNCR2820730108>3.0.CO;2-5
  20. Park, E. J., Park, H. R., Lee, J. S., and Kim, J., Licochalcone A: an inducer of cell differentiation and C$\gamma$totoxic agent from Pogostemon cablin. Planta Med., 64, 393-490 (1998) https://doi.org/10.1055/s-2006-957466
  21. Powis, G., Inhibitors of phospholipase C. Drugs Future, 18, 343-350 (1993)
  22. Rhee, S. G., Ryu, S. H., Lee, K. Y., and Cho, K. S., Assays of phosphoinositide specific phospholipase C and purification of isozymes from bovine brain. In Dennis, E. A., (Ed.), Methods in Enzymology, Academic Press, New York, Vol. 197, pp. 502-511 (1991)
  23. Rhee, S. G. and Bae, Y S., Regulation of phosphoinositidespecific phospholipase C isozymes. J. Biol Chem., 272, 15045-15048 (1997) https://doi.org/10.1074/jbc.272.24.15045
  24. Shimomura, H., Sashida, Y., and Oohara, M., Lignans from Machilus thunbergii. Phytochemistry, 26,1513-1515 (1987) https://doi.org/10.1016/S0031-9422(00)81847-6
  25. Shimomura, H., Sashida, Y., and Oohara, M., Lignans from Machilus thunbergii. Phytochemistry, 27, 634-636 (1988) https://doi.org/10.1016/0031-9422(88)83162-5
  26. Skehan, P., Storeng, R., Scudiero, D. A., Monks, A., McMahon, J., Waren, J., Bokesch, H., Kenney, S., and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst.,82,1107-1112 (1990) https://doi.org/10.1093/jnci/82.13.1107
  27. Yu, Y. U., Kang, S. Y, Park, H. Y., Sung, S. H., Lee, E. J., Kim, S. Y., and Kim, Y C., Antioxidant Iignans from Machilus thunbergii protect $CCl_4$-injured primary cultures of rat hepatocytes. J. Pharm. Pharmacol., 52,1163-1169(2000) https://doi.org/10.1211/0022357001774949