title: The apoptotic and autophagic properties of two natural occurring prodrugs, hyperoside and hypoxoside, against pancreatic cancer cell lines.
abstract: Pancreatic cancer is only the 12th most common cancer, but the fourth leading cause of cancer-related deaths in the world. This is due to late prognosis, poor response to chemotherapy and early metastases. Natural prodrugs may play an important role in the treatment of pancreatic cancer. The main aim of this study was to determine the cytotoxicity of five natural prodrugs, namely harpagoside, hyperoside, hypoxoside, oleuropein and polydatin, by investigating apoptosis and autophagy as possible mechanism/s of action. Hypoxoside and hyperoside have shown selective cytotoxicity at IC50 values of ∼25 and 50μM against INS-1 and MIA PaCa-2 pancreatic cancer cells, respectively. Hypoxoside and hyperoside induced G2/M phase arrest and caspase-3 activation in INS-1 and MIA PaCa-2 cells, respectively. Hoechst/phalloidin staining confirmed morphological changes, including condensed chromatin multinucleation, membrane blebbing and loss of cytoskeletal arrangement in INS-1 and MIA PaCa-2 cells. Acridine orange staining was absent in INS-1 (hypoxoside) and MIA PaCa-2 (hyperoside) treated cells, whereas LC3B expression was not significantly increased. INS-1 and MIA PaCa-2 treated cells favour the cell death pathway, apoptosis, over the cell survival pathway, autophagy.
authors.affiliation: Department of Biochemistry and Microbiology, Medicinal Plant and Natural Product Research Group, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031, South Africa.
authors.forename: Gerhardt J
authors.initials: GJ
authors.lastname: Boukes
authors.affiliation: Department of Biochemistry and Microbiology, Medicinal Plant and Natural Product Research Group, P.O. Box 77000, Nelson Mandela Metropolitan University, Port Elizabeth 6031, South Africa. Electronic address: maryna.vandeventer@nmmu.ac.za.
authors.forename: Maryna
authors.initials: M
authors.lastname: van de Venter
mesh_terms: D000165:Acridine Orange / Q000378:metabolism; D000480:Alkynes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000071182:Autophagosomes / Q000187:drug effects / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013194:Staining and Labeling
chemical_list: D000480:Alkynes; D014408:Biomarkers, Tumor; D005960:Glucosides; D008869:Microtubule-Associated Proteins; D011355:Prodrugs; C087941:hypoxoside; C021304:hyperoside; D004247:DNA; D011794:Quercetin; D053148:Caspase 3; D000165:Acridine Orange
keywords: Apoptosis; Autophagy; Harpagoside (PubChem CID: 5281542); Hyperoside; Hyperoside (PubChem CID: 5281643); Hypoxoside; Hypoxoside (PubChem CID: 6438448; INS-1; MIA PaCa-2; Oleuropein (PubChem CID: 5281544); Polydatin (PubChem CID: 5281718)