title: Viola plant cyclotide vigno 5 induces mitochondria-mediated apoptosis via cytochrome C release and caspases activation in cervical cancer cells.
abstract: Cyclotides describe a unique cyclic peptide family that displays a broad range of biological activities including uterotonic, anti-bacteria, anti-cancer and anti-HIV. The vigno cyclotides consist of vigno 1-10 were reported recently from Viola ignobilis. In the present study, we examined the effects of vigno 5, a natural cyclopeptide from V. ignobilis, on cervical cancer cells and the underlying mechanisms. We found that vigno 5-treated Hela cells were killed off by apoptosis in a dose-dependent manner within 24h, and were characterized by the appearance of nuclear shrinkage, cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation. The mitochondrial pathway of apoptosis revealed that cytochrome C is released from mitochondria to cytosol, associated with the activation of caspase-9 and -3, and the cleavage of poly (ADP-ribose) polymerase (PARP). Overall, the results indicate that vigno 5 induces apoptosis in part via the mitochondrial pathway, which is associated with a release of cytochrome C and elevated activity of caspase-9 and -3 in Hela cells.
authors.affiliation: Department of Biology, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G.C., Evin, Tehran, Iran.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Esmaeili
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G.C., Evin, Tehran, Iran.
authors.forename: Nazanin
authors.initials: N
authors.lastname: Abagheri-Mahabadi
authors.affiliation: Department of Chemistry, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Hashempour
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G.C., Evin, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Farhadpour
authors.affiliation: Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090, Vienna, Austria.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Gruber
authors.affiliation: Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, G.C., Evin, Tehran, Iran. Electronic address: a_ghassempour@yahoo.com.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ghassempour
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D047169:Cyclotides / Q000737:chemistry*; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry; D032413:Viola / Q000737:chemistry*
chemical_list: D047169:Cyclotides; D010940:Plant Proteins; C000608988:vigno 5 cyclotide, Viola ignobilis; D045304:Cytochromes c; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; Cyclotide; Mitochondrial pathway; Vigno 5; Viola ignobilis