Planta Med 2005; 71(5): 464-469
DOI: 10.1055/s-2005-864143
Original Paper
Natural Product Chemistry
© Georg Thieme Verlag KG Stuttgart · New York

Cytotoxicity of Neolignans Identified in Saururus chinensis towards Human Cancer Cell Lines

Jong-Cheon Hahm1 , In-Kyoung Lee2 , Won-Ki Kang2 , Soo-Un Kim3 , 4 , Young-Joon Ahn4
  • 1GN R&D Center, GreenTek21 Co., Sungnam, Republic of Korea
  • 2Division of Hematology/Oncology, Samsung Medical Center, Seoul, Republic of Korea
  • 3Plant Metabolism Research Center, Kyung Hee University, Yongin, Republic of Korea
  • 4School of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
Further Information

Publication History

Received: July 26, 2004

Accepted: January 3, 2005

Publication Date:
01 June 2005 (online)

Abstract

The cytotoxicity of compounds derived from the aerial parts of Saururus chinensis towards 24 cancer model and six normal cell lines was examined by MTT assay and compared with those of the anticancer agents cisplatin and doxorubicin. The active principles were characterized as the neolignans manassantin A, and its erythro,erythro- and threo,erythro-epimers by spectroscopic analysis. Manassantin A was isolated from S. chinensis as a new cytotoxic principle. Its two epimers were isolated for the first time in nature. The neolignans were more active than cisplatin and doxorubicin, with IC50 values of the neolignans, cisplatin, and doxorubicin against SK-Hep-1, PC-3, DU-145, BT-20, SK-BR-3, T-47D, Hela, T98G, and SK-MEL-28 cancer cell lines, in the ranges 0.018 - 0.423, 1.175 - 7.922, and 0.131 - >50 μg/mL, respectively. Manassantin A and its threo,erythro-epimer were equicytotoxic towards model cancer cell lines. threo,erythro-Manassantin A was more active than erythro,erythro-manassantin A. Additionally, these three neolignans (IC50 > 10 μg/mL) had very low cytotoxicity towards six normal cell lines, whereas cisplatin (IC50 2.846 - 0.825 μg/mL) and doxorubicin (IC50 5.222 - 0.008 μg/mL) exhibited potent cytotoxic effects. Structure-activity relationships indicate that the hydroxy moiety appears to be essential for cytotoxicity. These neolignans merit further study as potential anticancer agents or as leads.

References

  • 1 van der Bliek A M, Borst P. Multidrug resistance.  Adv Cancer Res. 1989;  52 165-204
  • 2 Stark G R. DNA amplification in drug resistant cells and in tumours.  Cancer Surv. 1986;  5 1-23
  • 3 Malpas J S. Chemotheraphy. Introduction to the Cellular and Molecular Biology of Cancer. Oxford; Oxford University Press 1991: pp 451-69
  • 4 Barclay A S, Perdue RE J r. Distribution of anticancer activity in higher plants.  Cancer Treat Rev. 1976;  50 1081-113
  • 5 Cassady J M, Douros J D. Anticancer Agents Based on Natural Product Models. New York; Academic Press 1980
  • 6 Kinghorn A D, Balandrin M F. Human Medicinal Agents from Plants. ACS Symposium Series 534. Washington, DC; American Chemical Society 1993
  • 7 Hamada T. Studies on ”Ishataoshi” and related names as a folk medicine in Japan.  J Med Pharmaceut Soc (WAKANYAKU). 1993;  10 104-9
  • 8 McLaughlin J L, Chang C J, Smith D L. Simple bench-top bioassays (brine shrimp and potato discs) for the discovery of plant antitumor compounds: review of recent progress. ACS Symposium Series 534. Washington, DC; American Chemical Society 1993: pp 112-37
  • 9 Alley M C, Scudiero D A, Monks A, Hursey M L, Czewinski M J, Fine D L, Abbott B J, Mayo J G, Shoemaker R H, Boyd M R. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay.  Cancer Res. 1988;  48 598-601
  • 10 Bruggisser R, von Daeniken K, Jundt G, Schaffner W, Tullberg-Reinert H. Interference of plant extracts, phytoestrogens and antioxidants with the MTT tetrazolium assay.  Planta Med. 2002;  68 445-8
  • 11 Rao K V, Alvarez F M. Manassantins A/B and saucerneol: novel biologically active lignoids from Saururus cernuus .  Tetraheadron Lett. 1983;  24 4947-50
  • 12 Kim T J. Korean Resources Plants. Seoul; Seoul National University Press 1996: pp 66-7
  • 13 Kwak J U. Pharmaceutical studies on Saururus chinensis Baill. PhD Dissertation. Suwon; Kyung Hee University 1988
  • 14 Choe K H, Yoon C H, Kwon S J. A study on chemical composition of Saururaceae growing in Korea (5), on flavonoid constituents of Saururus chinensis .  J Kor Soc Anal Sci. 1994;  7 11-5
  • 15 Jung D S. A study on the flavonoid components of Saururus chinensis .  J Basic Sci Cheju Nat University. 1995;  8 137-42
  • 16 Whang E C, Shih M H, Liu M C, Chen M T, Lee G H. Studies on constituents of Saururus chinensis .  Heterocycles. 1996;  43 969-75
  • 17 Choe K H, Kwon S J. A study on chemical composition of Saururaceae growing in Korea (2), on volatile constituents of Saururus chinensis by GC and GC-MS method.  J Kor Soc Anal Sci. 1988;  2 259-62
  • 18 Choe K H, Kwon S J. A study on essential oil of Houttuynia cordata and Saururus chinensis .  Thesis Collection, Kyung Hee University. 1989;  18 341-7
  • 19 Jung D S. Comparison on volatile constituents of Houttuynia cordata and Saururus chinensis by GC and GC-MS method.  Cheju Nat Univ J. 1991;  33 105-11
  • 20 Rao K V, Puri V N, Diwan P K, Alvarez F M. Preliminary evaluation of manassantin A, a potential neuroleptic agent from Saururus cernuus .  Pharmacol Res Commun. 1987;  19 629-38

Young-Joon Ahn, PhD

School of Agricultural Biotechnology

Seoul National University

Seoul 151-921

Republic of Korea

Fax: +82-2-873-2319

Email: yjahn@snu.ac.kr

    >