title: Pennogenyl Saponins from Paris quadrifolia L. Induce Extrinsic and Intrinsic Pathway of Apoptosis in Human Cervical Cancer HeLa Cells.
abstract: Pennogenyl saponins are the active compounds of large number of plant species and consequently many polyherbal formulations. Hence, great interest has been shown in their characterization and in the investigation of their pharmacological and biological properties, especially anticancer. This present study reports on the evaluation of cytotoxic effects and explanation of the molecular mechanisms of action of the two pennogenyl saponins (PS 1 and PS 2) isolated from Paris quadrifolia L. rhizomes on human cervical adenocarcinoma cell line HeLa. To determine the viability of the cells treated with the compounds we used real-time cell proliferation analysis and found that the pennogenyl saponins PS 1 and PS 2 strongly inhibited the tumor cells growth with IC50 values of 1.11 ± 0.04 μg/ml and 0.87 ± 0.05 μg/ml, respectively. The flow cytometry analysis indicated that the two compounds induced apoptosis in a dose-dependent manner and decreased mitochondrial membrane potential in HeLa cells in the early stage of apoptosis. Quantitative PCR and Western Blot analysis showed that the two saponins significantly increased mRNA expression of FADD and BID as well as induced caspase-8 via increased of procaspase-8 processing in the treated cells. The results of this study suggest that both the extrinsic death receptor and intrinsic mitochondrial pathways are involved in the programmed cell death.
authors: Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland.
authors: Justyna
authors: J
authors: Stefanowicz-Hajduk
authors: Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland.
authors: Rafal
authors: R
authors: Bartoszewski
authors: Department of Inorganic Chemistry, Medical University of Gdansk, Gdansk, Poland.
authors: Sylwia
authors: S
authors: Bartoszewska
authors: Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland.
authors: Kinga
authors: K
authors: Kochan
authors: Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland.
authors: Anna
authors: A
authors: Adamska
authors: Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland.
authors: Igor
authors: I
authors: Kosiński
authors: Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdansk, Poland.
authors: J Renata
authors: JR
authors: Ochocka
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051023:BH3 Interacting Domain Death Agonist Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053200:Fas-Associated Death Domain Protein / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D019668:Liliaceae / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D027343:Rhizome / Q000737:chemistry; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D012503:Saponins; D053181:Caspase 8