Cytotoxic Furanogermacranolides from the Flowers of Helianthus angustifolius

Abstract

The dichloromethane extract of the flowers of Helianthus angustifolius L. (Asteraceae, Heliantheae) was investigated in vitro for its cytotoxic activity using human cancer cell lines: CCRF-CEM leukemia, MDA-MB-231 breast cancer, U251 glioblastoma, HCT 116 colon cancer cells, and the human lung fibroblast cell line MRC-5. Cytotoxicity-guided fractionation led to the isolation of four related heliangolide-type sesquiterpene lactones. The structures were elucidated by means of NMR spectroscopy and high-resolution mass spectrometry. Of the investigated compounds, 8-methacrylyl-4,15-iso-atriplicolide (1) showed the highest activity against all tested cancer cell lines with IC₅₀ values ranging from 0.26 ± 0.01 µM for CCRF-CEM cells to 4.22 ± 0.26 µM for MRC-5 cells.

Helianthus angustifolius - Asteraceae - heliangolide - isoatriplicolide - cancer cell lines - MRC-5 lung fibroblast cells

References

• 1 Radford A E, Ahles H E, Bell C R. Manual of the vascular flora of the Carolinas. Chapel Hill: The University of North Carolina Press; 1964: 1113
• 2 Correll D S, Johnston M C. Manual of the vascular plants of Texas. Richardson: The University of Texas at Dallas; 1996: 1650-1653
• 3 Weakley A S. Flora of the Southern and Mid-Atlantic states working draft of 8 March 2010. University of North Carolina; 2010: 844-849
• 4 Ohno N, Mabry T J. Germacranolides in Helianthus mollis.  Phytochemistry. 1979;  18 1003-1006
• 5 Watanabe K, Ohno N, Yoshioka H, Gershenzon J, Mabry T J. Sesquiterpene lactones and diterpenoids from Helianthus argophyllus.  Phytochemistry. 1982;  21 709-713
• 6 Bohlmann F, Jakupovic J, Kin R M, Robinson H. Neue ent-Atisiren- und ent-Kaurensäure-Derivate aus Helianthus-Arten.  Phytochemistry. 1980;  19 863-868
• 7 Waddell T G. Hymenoxin a flavone from Helianthus angustifolius.  Phytochemistry. 1973;  12 2061
• 8 Ohno N, Gershenzon J, Neuman P, Mabry T J. Diterpene carboxylic acids and a heliangolide from Helianthus angustifolius.  Phytochemistry. 1981;  20 2393-2396
• 9 Zhang S, Won Y-K, Ong C-N, Shen H-M. Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms.  Curr Med Chem. 2005;  5 239-249
• 10 Kinghorn A D, Carcache-Blanco E J, Chai H-B, Orjala J, Farnsworth N R, Kramer R A, Rose W C, Emanuel S, Vite G D, Jarjoura J, Cope F O. Discovery of anticancer agents of diverse natural origin.  Pure Appl Chem. 2009;  81 1051-1063
• 11 Efferth T, Kahl S, Paulus K, Adams M, Rauh R, Boechzelt H, Hao X, Kaina B, Bauer R. Phytochemistry and pharmacogenomics of natural products derived from traditional Chinese medicine and Chinese materia medica with activity against tumor cells.  Mol Cancer Ther. 2008;  7 152-161
• 12 Gershenzon J, Mabry T J. Furanoheliangolides from Helianthus schweinitzii.  Phytochemistry. 1984;  23 2557-2559
• 13 Spring O. Sesquiterpene lactones from Helianthus tuberosus.  Phytochemistry. 1991;  30 519-522
• 14 Kupchan S M, Eakin M A, Thomas A M. Tumor inhibitors. 69. Structure-cytotoxicity relationships among the sesquiterpene lactones.  J Med Chem. 1971;  14 1147-1152
• 15 Lee K H, Huang E S, Piantadosi C, Pagano J S, Geissman T A. Cytotoxicity of sesquiterpene lactones.  Cancer Res. 1971;  31 1649-1654
• 16 Fischer N H, Lu T, Cantrell C L, Castañeda-Acosta J, Quijano L, Franzblau S G. Antimycobacterial evaluation of germacranolides in honour of Professor G.H. Neil Towers 75th birthday.  Phytochemistry. 1998;  49 559-564
• 17 Schmidt T J. Toxic activities of sesquiterpene lactones: structural and biochemical aspects.  Curr Org Chem. 1999;  3 577-608
• 18 Schmidt T J. Quantitative structure-cytotoxicity relationships within a series of helenanolide type sesquiterpene lactones.  Pharm Pharmacol Lett. 1999;  9 9-13
• 19 Seebacher W, Simic N, Weis R, Saf R, Kunert O. Spectral assignments of reference data.  Magn Reson Chem. 2003;  41 636-638
• 20 Scudiero D A, Shoemaker R H, Paull K D, Monks A, Tierney S, Nofziger T H, Currens M J, Seniff D, Boyd M. Evaluation of a soluble tetrazolium/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines.  Cancer Res. 1988;  48 4827-4833
• 21 Rinner B, Kretschmer N, Knausz H, Mayer A, Boechzelt H, Hao X J, Heubl G, Efferth T, Schaider H, Bauer R. A petrol ether extract of the roots of Onosma paniculatum induces cell death in a caspase dependent manner.  J Ethnopharmacol. 2010;  129 182-188