Isolation of a New 15-Membered Macrocyclic Glycolipid Lactone, Cuscutic Resinoside A from the Seeds of Cuscuta chinensis: A Stimulator of Breast Cancer Cell Proliferation

Abstract

While searching for new estrogenic compounds from the plant kingdom, we investigated an extract of the seeds of Cuscuta chinensis (Convolvulaceae) which showed potency for stimulating MCF-7 cell proliferation. A novel resin glycoside, cuscutic resinoside A (6) was isolated along with five known compounds from the extract. The structure was deduced from its spectral data as (11S)-hydroxyhexadecanoic acid 11-O-α-L-(4-O-2R,3R-nilylrhamnopyranosyl)-(1→2)-O-α-L-rhamnopyranosyl-(1,2-lactone) forming a unique 15-membered macrocyclic lactone. The compound significantly stimulated not only MCF-7 cell proliferation but also T47D human breast cancer cells at a concentration of 10 μM. Along with cuscutamine (1) and kaempferol (4), 6 was tested in the transient luciferase reporter assay and was found to have different luciferase inducing activity characteristics from the other compounds. These results suggest that 6 stimulated cancer cell proliferation by a different mechanism from 1 and 4.

MCF-7 cells - T47D cells - phytoestrogen - luciferase - Cuscuta chinensis - Convolvulaceae - seeds - resin glycoside

References

• 1 Zava D T, Blen M, Duwe G. Estrogenic activity of natural and synthetic estrogens in human breast cancer cells in culture.  Environ Health Perspect. 1997;  105 637
• 2 Soto A M, Sonnenschein C, Chung K L, Fernandez M F, Olea N, Serrano F O. The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants.  Environ Health Perspect. 1995;  103 113
• 3 Dictionary of Chinese Crude Drugs. ed by Jiangu S New Medical College, Shanghai Scientific Technologic Publisher Shanghai; 1977: p 2006
• 4 Miranda R P. Bioactive Natural Products from Traditionally Used Mexican Plants. In: Phytochemistry of Medicinal Plants. Arnason JT, Mata R, Romeo JT (eds.) Plenum Press New York; 1995: p 83
• 5 Miksicek R J. Interaction of naturally occurring nonsteroidal estrogens with expressed recombinant human estrogen receptor.  J Steroid Biochem Mol Biol. 1994;  49 153
• 6 Yahara S, Domoto H, Sugimura C, Nohara T, Niiho Y, Nakajima Y, Ito H. An alkaloid and two lignans from Cuscuta chinensis .  Phytochemistry. 1994;  37 1755
• 7 Miyazawa M, Kasahara H, Kameoka H. Biotransformation of lignans: Metabolism of (+)-eudesmin and (+)-magnolin in Spodoptera litura .  Phytochemistry. 1995;  39 1027
• 8 Wagner H, Mohan Chari V, Sonnenbichler J. ¹³C-NMR-Spektren Natuerlich vorkommender Flavonoide.  Tetrahedron Letters. 1976;  21 1799
• 9 Miyahara K, Du X M, Watanabe M, Sugimura C, Yahara S, Nohara T. Resin glycosides. XXIII. Two novel acylated trisaccharides related to resin glycoside from the seeds of Cuscuta chinensis .  Chem Pharm Bull. 1996;  44 481
• 10 Hara S, Okabe H, Mihashi K. Separation of aldose enantiomers by gas-liquid chromatography.  Chem Pharm Bull. 1986;  34 1843
• 11 Edmunds J S, Fairey E R, Ramsdell J S. A rapid and sensitive high throughput reporter gene assay for estrogenic effects of environmental contaminants.  Neurotoxicology. 1997;  18 525
• 12 Green S, Walter P, Kumar V, Krust A, Bornert J M, Argos P, Chambon P. Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A.  Nature. 1986;  320 134
• 13 Kuiper G G, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson J A. Cloning of a novel receptor expressed in rat prostate and ovary.  Proc Natl Acad Sci USA. 1996;  93 5925
• 14 Couse J F, Korach K S. Estrogen receptor null mice: what have we learned and where will they lead us?.  Endocrine Rev. 1999;  20 358
• 15 Vladusic E A, Hornby A E, Guerra-Vladusic F K, Lakins J, Lupu R. Expression and regulation of estrogen receptor beta in human breast tumors and cell lines.  Oncology Reports. 2000;  7 157
• 16 Mannich C, Schumann P. Jalap resin and its principal constituent convolvulin.  Arch Pharm Ber Dtsch Pharm Ges. 1938;  276 221
• 17 Ono M, Honda F, Karahashi A, Kawasaki T, Miyahara K. Resin glycosides. XXV. Multifidins I and II, new jalapins, from the seed of Quamoclit x multifida .  Chem Pharm Bull. 1997;  45 1955
• 18 Qian R Q, Meng Y. Modulation of tonic herbs on the immune cell inhibition in stressed model animal and its possible mechanism.  Zhongguo Zhong Yao Za Zhi. 2000;  25 169
• 19 Du X M, Kohinata K, Kawasaki T, Guo Y T, Miyahara K. Components of the ether-insoluble resin glycoside-like fraction from Cuscuta chinensis .  Phytochemistry. 1998;  48 843
• 20 Kitaoka M, Kadokawa H, Sugano M, Ichikawa K, Taki M, Takaishi S, Iijima Y, Tsutsumi S, Boriboon M, Akiyama T. A new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship.  Planta Medica. 1998;  64 511