title: Inula Viscosa Extracts Induces Telomere Shortening and Apoptosis in Cancer Cells and Overcome Drug Resistance.
abstract: Telomerase is activated in human papillomavirus (HPV) positive cervical cancer and targeting telomeres offers a novel anticancer therapeutic strategy. In this study, the telomere targeting properties, the cytotoxic as well as the pro-apoptotic effects of hexane (IV-HE) and dichloromethane (IV-DF) fractions from Inula viscosa L. extracts were investigated on human cervical HeLa and SiHa cancer cells. Our data demonstrate that IV-HE and IV-DF extracts were able to inhibit cell growth in HeLa and SiHa cells in a dose-dependent manner and studied resistant cell lines exhibited a resistance factor less than 2 when treated with the extracts. IV-HE and IV-DF extracts were able to inhibit telomerase activity and to induce telomere shortening as shown by telomeric repeat amplification protocol and TTAGGG telomere length assay, respectively. The sensitivity of fibroblasts to the extracts was increased when telomerase was expressed. Finally, IV-HE and IV-DF were able to induce apoptosis as evidenced by an increase in annexin-V labeling and caspase-3 activity. This study provides the first evidence that the IV-HE and IV-DF extracts from Inula viscosa L. target telomeres induce apoptosis and overcome drug resistance in tumor cells. Future studies will focus on the identification of the molecules involved in the anticancer activity.
authors.affiliation: a Laboratory of Biochemistry and Immunology, Faculty of Sciences, Rabat, Morocco Department of Biology and Medical Research CNESTEN, Rabat, Morocco and MEDyC CNRS UMR 7369, Faculty of Pharmacy , Reims , France.
authors.forename: Nawal
authors.initials: N
authors.lastname: Merghoub
authors.affiliation: b MEDyC CNRS UMR 7369, Faculty of Pharmacy , Reims , France.
authors.forename: Hassan
authors.initials: H
authors.lastname: El Btaouri
authors.affiliation: c Department of Biology and Medical Research CNESTEN , Rabat , Morocco.
authors.forename: Laila
authors.initials: L
authors.lastname: Benbacer
authors.affiliation: d Faculté des Sciences Ben M'sik , Casablanca , Morocco.
authors.forename: Saïd
authors.initials: S
authors.lastname: Gmouh
authors.affiliation: e MNHN, INSERM U565 and CNRS UMR 7196 , Paris , France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Trentesaux
authors.affiliation: f MEDyC CNRS UMR 7369, Faculty of Pharmacy , Reims , France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Brassart
authors.affiliation: g Cell and Tissue Imaging Platform (PICT IBISA) Reims , France.
authors.forename: Christine
authors.initials: C
authors.lastname: Terryn
authors.affiliation: h Department of Biology and Medical Research CNESTEN , Rabat , Morocco.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Attaleb
authors.affiliation: i MEDyC CNRS UMR 7369, Faculty of Pharmacy , Reims , France.
authors.forename: Claudie
authors.initials: C
authors.lastname: Madoulet
authors.affiliation: j Laboratory of Biochemistry and Immunology, Faculty of Sciences , Rabat , Morocco.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Benjouad
authors.affiliation: j Laboratory of Biochemistry and Immunology, Faculty of Sciences , Rabat , Morocco.
authors.forename: Saaïd
authors.initials: S
authors.lastname: Amzazi
authors.affiliation: k Department of Biology and Medical Research CNESTEN , Rabat , Morocco.
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Mzibri
authors.affiliation: l MEDyC CNRS UMR 7369, Faculty of Pharmacy , Reims , France.
authors.forename: Hamid
authors.initials: H
authors.lastname: Morjani
mesh_terms: D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D038143:Inula; D010936:Plant Extracts / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism; D059506:Telomere Shortening / Q000187:drug effects*
chemical_list: D017304:Annexin A5; D010936:Plant Extracts; D019098:Telomerase; D053148:Caspase 3