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

 

 Buy Article Permissions and Reprints

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.

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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 3 Dictionary of Chinese Crude Drugs. ed by Jiangu S New Medical College, Shanghai Scientific Technologic Publisher Shanghai; 1977: p 2006
  Google Scholar
• 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
  Google Scholar
• 5 Miksicek R J. Interaction of naturally occurring nonsteroidal estrogens with expressed recombinant human estrogen receptor.  J Steroid Biochem Mol Biol. 1994;  49 153
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 7 Miyazawa M, Kasahara H, Kameoka H. Biotransformation of lignans: Metabolism of (+)-eudesmin and (+)-magnolin in Spodoptera litura .  Phytochemistry. 1995;  39 1027
  CrossrefPubMedGoogle Scholar
• 8 Wagner H, Mohan Chari V, Sonnenbichler J. ¹³C-NMR-Spektren Natuerlich vorkommender Flavonoide.  Tetrahedron Letters. 1976;  21 1799
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 10 Hara S, Okabe H, Mihashi K. Separation of aldose enantiomers by gas-liquid chromatography.  Chem Pharm Bull. 1986;  34 1843
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 16 Mannich C, Schumann P. Jalap resin and its principal constituent convolvulin.  Arch Pharm Ber Dtsch Pharm Ges. 1938;  276 221
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar

Dr. Kaoru Umehara

School of Pharmaceutical Sciences

University of Shizuoka

52-1 Yada

Shizuoka 422-8526

Japan

Phone: +81-54-264-5661

Fax: +81-54-264-5661

Email: umehara@ys7.u-shizuoka-ken.ac.jp