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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Tomentosin Induces Telomere Shortening and Caspase-Dependant Apoptosis in Cervical Cancer Cells
Journal of Cellular Biochemistry, Volume 118, No. 7, Year 2017
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Description
Tomentosin, a natural sesquiterpene lactone purified from of Inula viscosa L., was investigated for its anti-proliferative, telomere shortening, and apoptotic effects on human cervical cancer HeLa and SiHa cell lines. Tomentosin was found to inhibit the growth of SiHa and HeLa cell lines in dose and time-dependent manner (IC50 values of 7.10 ± 0.78 μM and 5.87 ± 0.36 μM, respectively after 96 h of treatment). As evidenced by TTAGGG telomere length assay, tomentosin target specifically the telomeric overhang lengthening. This was confirmed by the evaluation of the cytotoxic effects of tomentosin in the foetal fibroblast Wi38 and JW10 cells which were derived from Wi38 and express hTERT, the telomerase catalytic subunit. We found that JW10 cells are 4.7-fold more sensitive to tomentosin which argues for telomere as its specific target. Furthermore, we found that tomentosin mediate this cytotoxic effect by inducing apoptosis and cell cycle arrest at G2/M phase. Morphological features of treated cells, as evidenced by Hoechst 33324 staining, revealed that the cytotoxic effect was due to induction of apoptosis. This was accompanied by pro-caspase-3 cleavage, an increase in caspase-3 activity and a cleavage of poly (ADP-ribose) polymerase (PARP). Moreover, tomentosin induced a decrease in mitochondrial membrane potential (ΔΨm) and an increase in reactive oxygen species (ROS), accompanied by a decrease in Bcl-2 expression. This indicates that tomentosin-induced apoptosis may involve a mitochondria-mediated signaling pathway. This study provides the first evidence that tomentosin targets telomere machinery and induces apoptosis in cervical cancer cells. The molecular mechanism underlying tomentosin-induced apoptosis may involve a mitochondria-mediated signaling pathway. J. Cell. Biochem. 118: 1689–1698, 2017. © 2016 Wiley Periodicals, Inc.
Authors & Co-Authors
Merghoub, Nawal
Morocco, Rabat
Faculté Des Sciences Rabat
Morocco, Rabat
National Energy Center of Nuclear Science and Technology
France, Reims
Matrice Extracellulaire et Dynamique Cellulaire Medyc
Morocco, Agdal Rabat
Innovation and Research
El Btaouri, Hassan
France, Reims
Matrice Extracellulaire et Dynamique Cellulaire Medyc
Benbacer, Laïla
Morocco, Rabat
National Energy Center of Nuclear Science and Technology
Gmouh, Saïd
Morocco, Rabat
Centre National Pour la Recherche Scientifique et Technique
Trentesaux, Chantal
France, Reims
Université de Reims Champagne-ardenne
Brassart, Bertrand
France, Reims
Matrice Extracellulaire et Dynamique Cellulaire Medyc
Attaleb, M.
Morocco, Rabat
National Energy Center of Nuclear Science and Technology
Madoulet, Claudie
France, Reims
Matrice Extracellulaire et Dynamique Cellulaire Medyc
Wenner, Thomas
France, Lyon
Laboratoire de Biologie et Modélisation de la Cellule
Amzazi, Saaid
Morocco, Rabat
Faculté Des Sciences Rabat
Morjani, Hamid
France, Reims
Matrice Extracellulaire et Dynamique Cellulaire Medyc
El-Mzibri, Mohammed E.
Morocco, Rabat
National Energy Center of Nuclear Science and Technology
Statistics
Citations: 35
Authors: 12
Affiliations: 7
Identifiers
Doi:
10.1002/jcb.25826
ISSN:
07302312
e-ISSN:
10974644
Research Areas
Cancer