ABSTRACT
Xanthohumol (X), isoxanthohumol (IX), 8-prenylnaringenin (8PN) and 6-prenylnaringenin (6PN), prenylflavonoids from hop (Humulus lupulus L.), were investigated for their cytotoxicity and the mechanism by which they exert cell death when incubated with prostate cancer cell lines PC-3 and DU145. All compounds induced cell death in the absence of caspase-3 activation and typical apoptotic morphological features. The general pan-caspase inhibitor zVAD-fmk could not protect this form of cell death. In addition, the formation of vacuoles was observed in PC-3 cells treated with IX and 6PN, and in DU145 treated with IX, 8PN and 6PN, which could suggest the induction of autophagy and consequent cell death. The results indicate that hop-derived prenylflavanones (IX, 8PN, 6PN), but not prenylchalcones (X) induce a caspase-independent form of cell death, suggested to be autophagy. Therefore, IX, 8PN and 6PN appear to be promising candidates for further investigation in prostate anticancer therapy.
Subject(s)
Caspases/metabolism , Flavonoids/pharmacology , Humulus/chemistry , Amino Acid Chloromethyl Ketones/pharmacology , Caspase 3/metabolism , Caspase Inhibitors , Cell Death/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Cysteine Proteinase Inhibitors/pharmacology , Dose-Response Relationship, Drug , Flavanones/chemistry , Flavanones/pharmacology , Flavonoids/chemistry , Humans , Male , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/pharmacology , Propiophenones/chemistry , Propiophenones/pharmacology , Prostatic Neoplasms/enzymology , Prostatic Neoplasms/pathology , Xanthones/chemistry , Xanthones/pharmacologyABSTRACT
BACKGROUND/AIMS: In the European Union, an elaborate legal framework regulates botanical products both under food and medicinal law. The decision as to which legal framework applies to an individual product may differ between the Member States. In the case of botanical food supplements, all food law provisions apply to their manufacturing, composition and marketing, including the new claims legislation. METHODS: Elements from EU and national law, scientific and other publications are brought together to investigate how to clarify the differentiation between the use of botanicals for medicinal and health-promoting purposes on a scientific basis. RESULTS: Guidance on the safety assessment and quality evaluation of botanicals is proposed in light of the different approaches described in the scientific literature with particular attention to the concept of long-term use as an integral part of safety evaluation. Guidance on claims substantiation is also included, taking into consideration the proposed legislation, the concept of long-term experience and grading of evidence. CONCLUSIONS: A model for safety and efficacy assessment of botanical food supplements in the EU is proposed, and should be taken into consideration in the development of legislation and scientific research on botanicals.
Subject(s)
Consumer Product Safety/legislation & jurisprudence , Dietary Supplements/standards , Plant Preparations/standards , Animals , Biomedical Enhancement/standards , Consumer Product Safety/standards , Decision Trees , Diet Therapy/standards , Dietary Supplements/adverse effects , Dose-Response Relationship, Drug , Drug Labeling , European Union , Evaluation Studies as Topic , Evidence-Based Medicine/standards , Food Labeling/legislation & jurisprudence , Health Promotion , Humans , Legislation, Food , Phytotherapy/standards , Plant Preparations/adverse effects , Plant Preparations/isolation & purification , Plant Preparations/therapeutic use , Plants, Toxic/adverse effects , Risk Assessment , Species SpecificityABSTRACT
Chalcones xanthohumol (X) and desmethylxanthohumol (DMX), present in hops (Humulus lupulus L.), and the corresponding flavanones isoxanthohumol (IX, from X), 8-prenylnaringenin (8-PN, from DMX), and 6-prenylnaringenin (6-PN, from DMX), have been examined in vitro for their anti-proliferative activity on human prostate cancer cells PC-3 and DU145. X proved to be the most active compound in inhibiting the growth of the cell lines with IC50 values of 12.3+/-1.1 microM for DU145 and 13.2+/-1.1 microM for PC-3. 6-PN was the second most active growth inhibitor, particularly in PC-3 cells (IC50 of 18.4+/-1.2 microM). 8-PN, a highly potent phytoestrogen, exhibited pronounced anti-proliferative effects on PC-3 and DU145 (IC50 of 33.5+/-1.0 and 43.1+/-1.2 microM, respectively), and IX gave comparable activities (IC50 of 45.2+/-1.1 microM for PC-3 and 47.4+/-1.1 microM for DU145). DMX was the least active compound. It was evidenced for the first time that this family of prenylated flavonoids from hops effectively inhibits proliferation of prostate cancer cells in vitro.
