Planta Med 2003; 69(1): 21-25
DOI: 10.1055/s-2003-37021
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Cytotoxic Activity and G2/M Cell Cycle Arrest Mediated by Antofine, A Phenanthroindolizidine Alkaloid Isolated from Cynanchum paniculatum

Sang Kook Lee1 , Kyung-Ae Nam1 , Yoen-Hoi Heo1
  • 1College of Pharmacy, Ewha Womans University, Korea
Further Information

Publication History

Received: May 3, 2002

Accepted: July 13, 2002

Publication Date:
04 February 2003 (online)

Abstract

Starting with an extract derived from the root of Cynanchum paniculatum Kitagawa (Asclepiadaceae) that was active in the process of inhibiting the growth of human cancer cells in culture, a phenanthroindolizidine alkaloid antofine was isolated and identified as an active principle (IC50 = 7.0 ± 0.2 ng/ml for A549, human lung cancer cells; IC50 = 8.6 ± 0.3 ng/ml for Col2, human colon cancer cells). Prompted by the high potency of cancer cell growth inhibition, additional action mechanism studies were performed with antofine. Utilizing cultured Col2 cells as a model, antofine induced arrest in the G2/M phase of the cell cycle after 48 h of incubation. With wash-out experiment, colony formation was also inhibited in a dose-dependent manner. These data suggest the potential of antofine to serve as a cancer chemotherapeutic agent by virtue of arresting the cell cycle.

References

  • 1 Cragg G M, Newman D J, Snader K M. Natural products in drug discovery and development.  J Nat Prod. 1977;  60 52-60
  • 2 Baker J T, Borris R P, Carte B. Natural product drug discovery and development: new perspectives on international collaboration.  J Nat Prod. 1995;  58 1325-57
  • 3 Cragg G M. Role of plants in the National Cancer Institute Drug Discovery and Development Program. A.D. Kinghorn, M.F. Balandrin (Eds.) Human Medicinal Agents from Plants, ACS Symposium Series N. 534. American Chemical Society Books Washington, DC; 1993: P. 80-95
  • 4 Wall M E, Wani M C. Camptothecin and analogues: synthesis, biological in vitro and in vivo activities and clinical possibilities. A.D. Kinghorn, M.F. Balandrin (Eds.) Human Medicinal Agents from Plants, ACS Symposium Series N. 534. American Chemical Society Books Washington, DC; 1993: P. 149-169
  • 5 Pezzuto J M. Plant-derived anticancer agents.  Biochem Pharmacol. 1997;  53 121-33
  • 6 Nam K A, Lee S K. Evaluation of cytotoxic potential of natural products in cultured human cancer cells.  Nat Prod Sci. 2000;  6 183-8
  • 7 Capo M, Saa J M. (-)-Antofine: a phenanthroindolizidine from Vincetoxicum nigrum .  J Nat Prod. 1989;  52 389-90
  • 8 Tanner U, Wiegrebe W. Alkaloids of Cynanchum vincetoxicum: Efficacy against MDA-MB-231 mammary carcinoma cells.  Arch Pharm (Weinheim). 1993;  326 67-72
  • 9 Baumgartner B, Erdelmeier C AJ, Wright A D, Rari T, Sticher O. An antimicrobial alkaloid from Ficus septica .  Phytochemistry. 1990;  29 3327-30
  • 10 Lee S K, Cui B, Mehta R R, Kinghorn A D, Pezzuto J M. Cytostatic mechanism and antitumor potential of novel 1H-cyclopenta[b]benzofuran lignans isolated from Aglaia elliptica .  Chemico-Biological Interact. 1998;  115 215-28
  • 11 Pisha E, Chai H, Lee I S, Chagwedera T E, Farnsworth N R, Cordell G A. et al . Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis.  Nat Med. 1995;  1 46-51
  • 12 Suffness M, Cordell GA. In The Alkaloids. Brossi A., Ed Academic Press Orlando FL; 1985 Vol. 25 Ch. 1. P. 3-355
  • 13 Rao K N, Bhattacharya R K, Venkatachalam S R. Thymidylate synthase activity in leukocytes from patients with chronic myelocytic leukemia and acute lymphocytic leukemia and its inhibition by phenanthroindolizidine alkaloids pergularine and tylophorinidine.  Cancer Lett. 1998;  128 183-8
  • 14 You P Z. Chinese Materica. Harwood Academic Publishers 1998: 270-8
  • 15 Huang M T. Mode of action tylocrebine: effects on protein and nucleic acid synthesis.  Mol Pharmacol. 1972;  8 538-50
  • 16 Himes R H, Kersey R H, Heller-Bettinger I, Samson F E. Action of the vinca alkaloids vincristine, vinblastine, and deacetyl vinblastine amide on microtubules in vitro .  Cancer Res. 1976;  36 3798-802
  • 17 Schiff P B, Fant J, Horwiz S B. Promotion of microtubule assembly in vitro by taxol.  Nature. 1979;  277 655-7
  • 18 Eileen R, Wilforedo M, Eric J H, Tej K P, Charles R G. Paclitaxel sensitivity correlated with p53 status and DNA fragmentation, but not G2/M accumulation.  Int J Rad Oncol Biol Physics. 1999;  44 1119-24
  • 19 Taron M, Plasencia C, Abad A, Martin C, Guillot M. Cytotoxic effects of topotecan combined with various active G2/M-phase anticancer drugs in human tumor-derived cell lines.  Invest New Drugs. 2000;  18 139-47
  • 20 Makoto S, Yoshio H, Hisashi M, Toshitaka G, Tadaichi K, Kazuki K. Butyrolactone I induces cyclin B1 and causes G2/M arrest and skipping of mitosis in human prostate cell lines.  Cancer Lett. 1999;  138 121-30
  • 21 Konstantinos T P, Dimitra Z, Ourania T K, Emmanuel S P, Vasiliki V, George D G. et al . Protein tyrosine kinase inhibitor, genistein, enhances apoptosis and cell cycle arrest in K562 cells treated with γ-irradiation.  Cancer Lett. 2000;  160 107-13
  • 22 Zhang X W, Jiang J F, Xu B. Differentiation-inducing action of 10-hydroxycamptothecin on human hepatoma Hep G2 cells.  Acta Pharmacol Sin. 2000;  21 364-8

Dr. Sang Kook Lee

College of Pharmacy

Ewha Womans University

11-1 Daehyun-dong

Seodaemun-ku

Seoul 120-750

Korea

Phone: +82-2-3277-3023

Fax: +82-2-3277-2851

Email: sklee@mm.ewha.ac.kr