Nutr Cancer. 2016 Jan 15:1-13. [Epub ahead of print]

Inula Viscosa Extracts Induces Telomere Shortening and Apoptosis in Cancer Cells and Overcome Drug Resistance.

Merghoub N1, Btaouri HE2, Benbacer L3, Gmouh S4, Trentesaux C5, Brassart B6, Terryn C7, Attaleb M8, Madoulet C9, Benjouad A10, Amzazi S10, Mzibri ME11, Morjani H12.

• 1a 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.
• 2b MEDyC CNRS UMR 7369, Faculty of Pharmacy , Reims , France.
• 3c Department of Biology and Medical Research CNESTEN , Rabat , Morocco.
• 4d Faculté des Sciences Ben M'sik , Casablanca , Morocco.
• 5e MNHN, INSERM U565 and CNRS UMR 7196 , Paris , France.
• 6f MEDyC CNRS UMR 7369, Faculty of Pharmacy , Reims , France.
• 7g Cell and Tissue Imaging Platform (PICT IBISA) Reims , France.
• 8h Department of Biology and Medical Research CNESTEN , Rabat , Morocco.
• 9i MEDyC CNRS UMR 7369, Faculty of Pharmacy , Reims , France.
• 10j Laboratory of Biochemistry and Immunology, Faculty of Sciences , Rabat , Morocco.
• 11k Department of Biology and Medical Research CNESTEN , Rabat , Morocco.
• 12l MEDyC CNRS UMR 7369, Faculty of Pharmacy , Reims , France.

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.

PMID:  26771897