Browse > Article

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)
Publication Information
Archives of Pharmacal Research / v.27, no.10, 2004 , pp. 1043-1047 More about this Journal
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
Machilus thunbergii; Lauraceae; Phospholipase $C{\Upsilon}1$; Lignan; Flavan; Methylene dioxy group; Antiproliferation of human cancer cells;
Citations & Related Records

Times Cited By Web Of Science : 8  (Related Records In Web of Science)
Times Cited By SCOPUS : 7
연도 인용수 순위
1 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)   DOI   ScienceOn
2 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)   DOI   ScienceOn
3 Holloway, D. and Scheinmann, F., Two lignans from Litsea grandis and L. gracilipes. Phytochemistry, 13, 1233-1236 (1974)   DOI   ScienceOn
4 Kim, J. K., Illustrated Natural Drugs Encyclopedia, Namsandang, Seoul, Vol. 2. p. 48 (1984).
5 Lee, J. S., Cho, Y S., Park, E. J., Kim, J., Oh, W. K., Lee, H. S., and Ahn, J. S., Phospholipase C$\gamma$1 inhibitory principles from the sarcotestas of Ginkgo biloba. J. Nat. Prod., 61,867-872 (1998)   DOI   ScienceOn
6 Lee, J. S., Cho, Y S., Kim, J., Lee, H. S., and Ahn, J. S., Phospholipase C$\gamma$1 inhibitory principles from the sarcotestas of Ginkgo biloba (2). Kor. J. Pharmacogn., 30, 280-283 (1999a)
7 Skehan, P., Storeng, R., Scudiero, D. A., Monks, A., McMahon, J., Waren, J., Bokesch, H., Kenney, S., and Boyd, M. R., New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst.,82,1107-1112 (1990)   DOI   PUBMED
8 Berridge, M. J., Inositol triphosphate and calcium signaling. Nature, 361,315-325 (1993)   DOI   PUBMED   ScienceOn
9 Lee, J. S., Park, S. Y, Kim, J. Y, Oh, W. K., Lee, H. S., Ahn, J. S., and Kim, J., Isolation of phospholipase C$\gamma$1 inhibitors from Anemarrhena asphodeloides. Seoul Natl. Univ. J. Pharm. Sci, 21, 30-42 (1996a)
10 Lee, J. S., Kim, J., Kim, B. Y, Lee, H. S., and Ahn, J. S., Inhibition of phospholipase C$\gamma$1 and cancer cell proliferation by triterpene esters from Uncaria rhynchophylla. J. Nat. Prod., 63, 753-756 (2000)   DOI   ScienceOn
11 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)   DOI   ScienceOn
12 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)   DOI
13 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)   DOI   ScienceOn
14 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)   PUBMED
15 Nishizuka, Y, Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science, 258, 607-614 (1992)   DOI   PUBMED
16 Rhee, S. G. and Bae, Y S., Regulation of phosphoinositidespecific phospholipase C isozymes. J. Biol Chem., 272, 15045-15048 (1997)   DOI   ScienceOn
17 Shimomura, H., Sashida, Y., and Oohara, M., Lignans from Machilus thunbergii. Phytochemistry, 27, 634-636 (1988)   DOI   ScienceOn
18 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)   DOI   ScienceOn
19 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)   DOI   PUBMED   ScienceOn
20 Miyamura, M., Nohara, T., Tomimatsu, T., and Nishioka, I., Seven aromatic compounds from bark of Cinnamomum cassia. Phytochemistry, 22, 215-218 (1983)   DOI   ScienceOn
21 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)   DOI
22 Powis, G., Inhibitors of phospholipase C. Drugs Future, 18, 343-350 (1993)
23 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$1 activity by amentoflavone isolated from Selaginella tamariscina. Planta Med., 62, 293-296 (1996b)   DOI   ScienceOn
24 Shimomura, H., Sashida, Y., and Oohara, M., Lignans from Machilus thunbergii. Phytochemistry, 26,1513-1515 (1987)   DOI   ScienceOn
25 Noh, D. Y., Lee, Y. H., Kim, S. S., Kim, Y. I., Ryu, S. H., SUh, P. G., and Park, J. G., Elevated content of phospholipase C$\gamma$1 in colorectal cancer tissues. Cancer, 73, 36-41 (1994)   DOI   ScienceOn
26 Rhee, S. G., Ryu, S. H., Lee, K. Y., and Cho, K. S., Assays of phosphoinositide specific phospholipase C and purification of isozymes from bovine brain. In Dennis, E. A., (Ed.), Methods in Enzymology, Academic Press, New York, Vol. 197, pp. 502-511 (1991)
27 Lee, J. S., Yang, M. Y, Yeo, H., Kim, J., Lee, H. S., and Ahn, J. S., Uncarinic acids, phospholipase C$\gamma$1 inhibitors from hooks of Uncaria rhynchophylla. Bioorg. Med. Chem. Lett., 9, 1429-1432 (1999b)   DOI   PUBMED   ScienceOn