In vitro anti-neoplastic activity of the ethno-pharmaceutical plant Hypericum adenotrichum Spach endemic to Western Turkey

Abstract

Abstract. Hypericum perforatum (St. John's wort) is wellestablished for its antidepressant activity throughout the world and also various other species within this genus are used in different folk medicines. Hyperforin of St. John's wort inhibited growth of cancer cell lines and the use of hypericin (another compound of H. perforatum) in cancer photodynamic therapy is proposed. Therefore, we investigated the anti-cancer properties of H. adenotrichum Spach (Guttiferae), an endemic species in Turkey called 'kantaron', which is used for wound healing and antiseptic effects. Freeze-dried plant was extracted with petroleum ether, dichloromethane, ethyl acetate, and methanol and the bioactivity of these extracts was analysed by proliferation assay, cell death determination, by investigating protein expression profiles specific for cell cycle arrest and apoptosis as well as composition by HPLC. The strongest anti-proliferative activity was determined for the petroleum ether extract with an I p C 50 of ~5.8 μg/ml medium (referring to 1 mg dried plant) which correlated with cyclin D1 suppression and p21 induction. This extract also induced phosphorylation of H2AX, and activated caspase-3 followed by signature-type cleavage of PARP resulting in ~50% apoptosis at 23.2 μg/ml after 24 h of treatment. Neither hyperforin, hypericin, or amentoflavone contributed to these properties. To the best of our knowledge, we report for the first time that the endemic plant H. adenotrichum Spach exhibits potent p53-independent anti-neoplastic properties due to yet unexplored Hypericum constituents. IntroductionSome 60% of all drugs used in Western medicine are derived from natural compounds which served as leads (1). From the 80's up to now pharmaceutical companies collect marine organisms, bacteria, fungi and plants at random to test them in robot-screenings regarding their anti-cancer, anti-inflammatory, anti-bacterial etc. activities. Another approach requests the ancient ethno-botanical knowledge of old civilizations which mostly base on the in depth and long lasting empirical experiences with the locally available natural resources, plants at most.Of the 12,000 plant species in Europe under consideration approximately 11,500 taxa are found in Turkey alone with 33% of these plants endemic. Since numerous ancient civilisations lived in the area, the plant societies were tested for medicinal applications throughout the ages and many plant species are still used in Turkish folk medicine to treat various diseases (2).The rich botanical biodiversity of this region paired with the cultural background was the reason to explore the traditional healing plant Hypericum adenotrichum, one of 43 Hypericum species endemic in Turkey. Within the genus Hypericum various species are used in different folk medicines worldwide and are tested against cancer cell growth.The genus Hypericum is called 'kantaron' in Turkey and H. adenotrichum is used in folk medicine for antispasmodic and antiseptic effects, and wound healing especially burns (2). The use of ...