Neoandrographolide from Andrographis paniculata as a Potential Natural Chemosensitizer

 

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Abstract

Extracts of the traditional medicinal herb Andrographis paniculata and its main constituents are described in the literature as showing anticancer activity. The aim of this study was to isolate the main constituents of a commercially available phytotherapeutic preparation of A. paniculata and to determine their chemosensitizing potential in a leukemia cell line. Chromatographic separation steps resulted in the isolation of the diterpenes andrographolide (1) and 14-deoxy-11,12-didehydroandrographolide (3) and the diterpene glucoside neoandrographolide (2). The combination of these constituents with suboptimal concentrations of etoposide revealed compound 2 as chemosensitizer in S-Jurkat and X chromosome-linked inhibitor of apoptosis protein (XIAP)-overexpressing Jurkat cells, a model for chemoresistance.

References

• 1 Tang W, Eisenbrand G. Andrographis paniculata (Burm. f.) Nees.  Tang W, Eisenbrand G Chinese drugs of plant origin. Berlin, Heidelberg; Springer-Verlag 1992: 97-103
  PubMedGoogle Scholar
• 2 Matsuda T, Kuroyanagi M, Sugiyama S, Umehara K, Ueno A, Nishi K. Cell differentiation-inducing diterpenes from Andrographis paniculata Nees.  Chem Pharm Bull. 1994;  42 1216-1225
  CrossrefPubMedGoogle Scholar
• 3 Kumar R A, Sridevi K, Kumar N V, Nanduri S, Rajagopal S. Anticancer and immunostimulatory compounds from Andrographis paniculata.  J Ethnopharmacol. 2004;  92 291-295
  CrossrefPubMedGoogle Scholar
• 4 Cheung H-Y, Cheung S-H, Li J, Cheung C-S, Lai W-P, Fong W-F, Leung F-M. Andrographolide isolated from Andrographis paniculata induces cell cycle arrest and mitochondrial-mediated apoptosis in human leukemic HL-60 cells.  Planta Med. 2005;  71 1106-1111
  Article in Thieme ConnectPubMedGoogle Scholar
• 5 Yang L, Wu D, Luo K, Wu S, Wu P. Andrographolide enhances 5-fluorouracil-induced apoptosis via caspase-8-dependent mitochondrial pathway involving p 53 participation in hepatocellular carcinoma (SMMC-7721) cells.  Cancer Lett. 2009;  276 180-188
  CrossrefPubMedGoogle Scholar
• 6 Zhou J, Lu G-D, Ong C-S, Ong C-N, Shen H-M. Andrographolide sensitizes cancer cells to TRAIL-induced apoptosis via p 53-mediated death receptor 4 up-regulation.  Mol Cancer Ther. 2008;  7 2170-2180
  CrossrefPubMedGoogle Scholar
• 7 Fujita T, Fujitani R, Takeda Y, Takaishi Y, Yamada T, Kido M, Miura I. On the diterpenoids of Andrographis paniculata: X-ray crystallographic analysis of andrographolide and structure determination of new minor diterpenoids.  Chem Pharm Bull. 1984;  32 2117-2125
  CrossrefPubMedGoogle Scholar
• 8 Tan M L, Kuroyanagi M, Sulaiman S F, Najimudin N, Tengku Muhammad T S. Cytotoxic activities of major diterpenoid constituents of Andrographis paniculata in a panel of human tumor cell lines.  Pharm Biol. 2005;  43 501-508
  CrossrefPubMedGoogle Scholar
• 9 Wilkinson J C, Cepero E, Boise L H, Duckett C S. Upstream regulatory role for XIAP in receptor-mediated apoptosis.  Mol Cell Biol. 2004;  24 7003-7014
  CrossrefPubMedGoogle Scholar
• 10 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
  CrossrefPubMedGoogle Scholar
• 11 Nicoletti I, Migliorati G, Pagliacci M C, Grignani F, Riccardi C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry.  J Immunol Methods. 1991;  139 271-279
  CrossrefPubMedGoogle Scholar
• 12 Greco W R, Bravo G, Parsons J C. The search for synergy: a critical review from a response surface perspective.  Pharmacol Rev. 1995;  47 331-385
  PubMedGoogle Scholar

Prof. Dr. Hermann Stuppner

Institute of Pharmacy/Pharmacognosy
Center for Molecular Biosciences Innsbruck
Leopold-Franzens University of Innsbruck

Innrain 52c, Josef-Moeller-Haus

6020 Innsbruck

Austria

Phone: + 43 51 25 07 53 00

Fax: + 43 51 25 07 29 39

Email: hermann.stuppner@uibk.ac.at

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