Original Paper Pharmacology	Planta Med 2005; 71: 1030-1035 DOI: 10.1055/s-2005-873127
© Georg Thieme Verlag KG Stuttgart · New York
The Lipophilic Extract of Hypericum perforatum Exerts Significant Cytotoxic Activity Against T24 and NBT-II Urinary Bladder Tumor Cells
Dimitris Skalkos1, Nikolaos E. Stavropoulos2, Ioannis Tsimaris2, Eleni Gioti3, Constantine D. Stalikas3, Unyime O. Nseyo4, Elli Ioachim5, Niki J. Agnantis5
1 Department of Material Sciences & Engineering, University of Ioannina, Ioannina, Greece 2 Urology Department, ‘G. Hatzikosta' General Hospital, Ioannina, Greece 3 Laboratory of Analytical Chemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece 4 Division of Urology, Medical College of Virginia, Commonwealth University, Richmond, Virginia, USA 5 Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece

Abstract

Hypericum perforatum L. (St. John's wort) is a medicinal plant used for many pathologies, especially for the treatment of mild to moderate depression. In the present study we have investigated the cytotoxic activity of the locally collected (Epirus region) Hypericum perforatum L. against cultured T24 and NBT-II bladder cancer cell lines. The lipophilic extract of the herb, prepared using petroleum ether, induced apoptosis displaying LC₅₀ values at concentrations as low as 4 and 5 μg/mL. A fraction of this extract displayed 60 % cell growth inhibition at a concentration of 0.95 μg/mL. Evaluating the importance of various biologically active components of the extract, it was found that hypericins (hypericin, pseudohypericin, etc.) were identified only in the methanolic (lipophobic) extract of the herb, and not in the active lipophilic extract. In addition, hyperforin concentrations in the lipophilic extract and its most active fraction, were 0.94 μg/mL, and 0.17 μg/mL, respectively, while the active cytotoxic concentration of pure hyperforin appeared in the range of 1.8 μg/mL - 5.0 μg/mL. Therefore, pure hyperforin does not seem to contribute significantly to the cytotoxicity activity. Chlorophylls were identified in low, not significantly different, concentrations in all extracts and fractions and were not correlated to the biological activity.

Owing to the combination of significant cytotoxic activity, natural abundance and low toxicity, the lipophilic extract of Hypericum perforatum holds the promise of being an interesting, new, antiproliferative agent against bladder cancer that deserves further investigation.

Abbreviations

HP:Hypericum perforatum L.

AS:aqueous solution

MS:methanolic solution

ME:methanolic extract

NPMF:non polar methanolic fraction

PMF:polar methanolic fraction

PEE:petroleum ether (lipophilic) extract

PEE (1,2,3,4,5,6,7):petroleum ether extract's fractions

PBS:phosphate buffered saline

DMSO:dimethyl sulfoxide

Key Words

Hypericum perforatum L. - St. John's wort - hypericin - pseudohypericin - hyperforin - chlorophylls - bladder tumor