title: Oenothera paradoxa defatted seeds extract containing pentagalloylglucose and procyanidins potentiates the cytotoxicity of vincristine.
abstract: The purpose of the study was a comparison of Oenothera paradoxa Hudziok defatted seeds extract (EPE) effect with the activity of individual constituents of the extract: pentagalloylglucose (PGG), gallic acid, (+)-catechin and the procyanidin fraction, as well as an assessment of the combined effect of EPE and vincristine (VCR) in the absence or presence of MRP1 (indomethacin) and P-glycoprotein (verapamil) inhibitors, on two human cancer cell lines, metastatic melanoma (HTB-140) and hepatoma (HepG2). The presence of EPE, PGG and procyanidins caused a marked reduction in viability (MTT assay) and rise in mortality (LDH release assay) of HTB-140 cells. The combined use of EPE (25 μg/mL) and VCR (1 μM) in HTB-140 and HepG2 cells produced an increased cytotoxicity as compared to vincristine alone - by more than 4 and 1.5 times, respectively. In HTB-140 cells, the level of intracellular ATP (measured by bioluminescence) was lowered over 7-fold as a result of exposure to the combination of EPE and VCR, while the addition of MRP-1 inhibitor did not cause an increased cytotoxicity or further lowering of the ATP level. Our results demonstrate that EPE, containing PGG and procyanidins, significantly increased the sensitivity of cancer cells, particularly the melanoma cells, to the action of vincristine.
authors.affiliation: Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Jaszewska
authors.forename: A
authors.initials: A
authors.lastname: Kosmider
authors.forename: A K
authors.initials: AK
authors.lastname: Kiss
authors.forename: M
authors.initials: M
authors.lastname: Naruszewicz
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005707:Gallic Acid / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D047348:Hydrolyzable Tannins / Q000009:adverse effects / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors; D031664:Oenothera; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000009:adverse effects / Q000494:pharmacology; D012639:Seeds; D014750:Vincristine / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000255:Adenosine Triphosphate; D000972:Antineoplastic Agents, Phytogenic; D002392:Catechin; D005707:Gallic Acid; D047348:Hydrolyzable Tannins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010936:Plant Extracts; D044945:Proanthocyanidins; D014750:Vincristine; C435084:pentagalloylglucose; C421109:multidrug resistance-associated protein 1