Abstract
Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is a multifunctional oleanane synthetic triterpenoid with potent anti-inflammatory and antitumorigenic properties. The mechanisms of the antisurvival and apoptosis-inducing activities of CDDO-Me and related derivatives of oleanolic acid have been defined; however, to date, no study has been carried out on the effect of CDDOs on human telomerase reverse transcriptase (hTERT) gene or telomerase activity. Here we report for the first time that inhibition of cell proliferation and induction of apoptosis by CDDO-Me in pancreatic cancer cell lines is associated with the inhibition of hTERT gene expression, hTERT telomerase activity and a number of proteins that regulate hTERT expression and activity. Furthermore, abrogation or overexpression of hTERT protein altered the susceptibility of tumor cells to CDDO-Me. These findings suggest that telomerase (hTERT) is a relevant target of CDDO-Me in pancreatic cancer cells.
Original language | English (US) |
---|---|
Pages (from-to) | 561-567 |
Number of pages | 7 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 422 |
Issue number | 4 |
DOIs | |
State | Published - Jun 15 2012 |
Externally published | Yes |
Keywords
- Akt (protein kinase b)
- Apoptosis
- CDDO-Me
- HTERT
- MTS
- NF-κB
- PARP-1
- Pancreatic cancer
- STAT-3
- Telomerase
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology