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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
Published on: April 13, 2015
Inula Viscosa Extracts Induces Telomere Shortening and Apoptosis in Cancer Cells and Overcome Drug Resistance
Nawal Merghoub1, Hassan El Btaouri2, Laila Benbacer3
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.
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.
Insights
Inula viscosa L. extracts (IV-HE and IV-DF) show anticancer potential by inhibiting telomerase activity and inducing telomere shortening in cervical cancer cells. These extracts also promote apoptosis and overcome drug resistance, offering a novel therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Telomerase activation is common in human papillomavirus (HPV)-positive cervical cancer.
- Targeting telomeres presents a novel therapeutic strategy for cancer treatment.
- Inula viscosa L. extracts are being investigated for their medicinal properties.
Purpose of the Study:
- To investigate the telomere targeting, cytotoxic, and pro-apoptotic effects of Inula viscosa L. hexane (IV-HE) and dichloromethane (IV-DF) fractions.
- To evaluate the efficacy of these extracts on human cervical cancer cell lines (HeLa and SiHa).
- To assess the potential of these extracts in overcoming drug resistance and inducing apoptosis.
Main Methods:
- Cell growth inhibition assays were performed on HeLa and SiHa cells.
- Telomere targeting was assessed using telomeric repeat amplification protocol (TRAP) and telomere length assays.
- Apoptosis was evaluated through annexin-V labeling and caspase-3 activity measurements.
Main Results:
- IV-HE and IV-DF extracts inhibited cell growth in a dose-dependent manner.
- Extracts effectively inhibited telomerase activity and induced telomere shortening.
- Increased sensitivity to extracts was observed in fibroblasts expressing telomerase.
- Apoptosis was induced, as evidenced by increased annexin-V labeling and caspase-3 activity.
- Drug resistance factor was less than 2 in treated cell lines.
Conclusions:
- IV-HE and IV-DF extracts from Inula viscosa L. demonstrate significant anticancer activity against cervical cancer cells.
- These extracts target telomeres, inhibit telomerase, induce apoptosis, and overcome drug resistance.
- This study provides the first evidence of these specific effects for Inula viscosa L. extracts.
- Further research is warranted to identify the active molecules responsible for the observed anticancer effects.
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