Premium
Caloric Restriction Decreases Telomerase Activity and Enhances BIBR 1532 Inhibition Response on MDA‐MB 231 Cell Line
Author(s) -
Hilal George Y,
Alaaeddine Nada,
Wardi Layal,
Assad Chafika
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.915.10
Subject(s) - telomerase , telomerase reverse transcriptase , telomere , cell growth , microbiology and biotechnology , cell culture , biology , chemistry , cancer research , biochemistry , dna , genetics , gene
The metabolism of cancer cells is modulated by the nutrients content in their environment. Caloric restriction (CR) decreases proliferation, promotes differentiation, and transformation to quiescent cells. The immortality of cancerous cells is largely assured by the telomerase, an interesting target for inhibition by BIBR 1532. One obstacle faces the outcome of this inhibition is the long lag phase due to abnormal telomere length. In this study, we investigated the effect of CR on telomerase activity and its response to BIBR 1532. Breast cancer MDA‐MB 231 cells were cultured in DMEM with 0, 1 or 4.5 g/l of glucose. The telomerase activity was measured by quantitative Real‐Time PCR, the two telomerase subunits were semi quantified by RT‐PCR. Proliferation test and mitochondrial metabolism were assessed by tetrazolium salt oxidation and cell counts. CR decreased telomerase activity by 60% and enhanced cells response to 2.5 μM of BIBR 1532 without any modification in the expression of its two subunits hTERT (Reverse Transcriptase) and hTR (RNA Template) mRNA. BIBR1532 significantly decreased mitochondrial metabolism in dose dependent manner in cells cultured with 1 and 4.5 g/L of glucose. Taken together, our results demonstrated that CR decreases telomerase activity and mitochondrial metabolism which are directly modulated by BIBR 1532. This work was supported by the research council of Saint‐Joseph University.