title: Lclet 4 enhances pro-apoptotic and anti-invasive effects of mitoxantrone on human prostate cancer cells - in vitro study.
abstract: Triterpene saponosides are widely distributed plant secondary metabolites characterized by relatively low systemic cytotoxicity and a range of biological activities. These include anti-inflammatory, antimicrobial, vasoprotective and antitumor properties. In particular, the ability of saponins to enhance the cytotoxicity of chemotherapeutic drugs opened perspectives for their application in combined cancer chemotherapy. Here, we used human prostate cancer DU-145 cells as an in vitro model to elucidate the synergy of the interactions between biological activities of an oleanane type 13β,28-epoxy triterpene saponoside (Lclet 4) and mitoxantrone, which is a cytostatic drug commonly used in prostate cancer therapy. No cytotoxic or pro-apoptotic effect of Lclet 4 and mitoxantrone administered at the concentrations between 0.05 and 0.1 µg/ml could be seen. In contrast, cocktails of these agents exerted synergistic pro-apoptotic effects, accompanied by the activation of the caspase 3/7 system. This effect was paralleled by attenuating effects of Lclet 4/mitoxantrone cocktails on the invasive potential, metalloproteinase expression and motility of DU-145 cells. Multifaceted and additive effects of Lclet 4 and mitoxantrone on basic cellular traits crucial for prostate cancer progression indicate that the combined application of both agents at systemically neutral concentrations may provide the basis for new promising strategies of prostate cancer chemotherapy.
authors.affiliation: Department of Cell Biology, Faculty of Biochemistry, Biophysics and Biotechnology, and Department of Pharmacognosy, Faculty of Pharmacy, Medical College, Jagiellonian University, Kraków, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Koczurkiewicz
authors.forename: Irma
authors.initials: I
authors.lastname: Podolak
authors.forename: Katarzyna Anna
authors.initials: KA
authors.lastname: Wójcik
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Galanty
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Madeja
authors.forename: Marta
authors.initials: M
authors.lastname: Michalik
authors.forename: Jarosław
authors.initials: J
authors.lastname: Czyż
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053179:Caspase 7 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015870:Gene Expression; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D008942:Mitoxantrone / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry*; D018517:Plant Roots / Q000737:chemistry*; D029623:Primulaceae / Q000737:chemistry*; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: C587956:13beta,28-epoxy triterpene saponoside; D000970:Antineoplastic Agents; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; D008942:Mitoxantrone; D045726:Metalloproteases; D053148:Caspase 3; D053179:Caspase 7