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 |
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Keywords
- Akt (protein kinase b)
- Apoptosis
- CDDO-Me
- HTERT
- MTS
- NF-κB
- PARP-1
- Pancreatic cancer
- STAT-3
- Telomerase
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Molecular Biology
Cite this
Inhibition of cell proliferation and induction of apoptosis by oleanane triterpenoid (CDDO-Me) in pancreatic cancer cells is associated with the suppression of hTERT gene expression and its telomerase activity. / Deeb, Dorrah; Gao, Xiaohua; Liu, Yongbo; Kim, Sahn Ho; Pindolia, Kirit R.; Arbab, Ali Syed; Gautam, Subhash C.
In: Biochemical and Biophysical Research Communications, Vol. 422, No. 4, 15.06.2012, p. 561-567.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inhibition of cell proliferation and induction of apoptosis by oleanane triterpenoid (CDDO-Me) in pancreatic cancer cells is associated with the suppression of hTERT gene expression and its telomerase activity
AU - Deeb, Dorrah
AU - Gao, Xiaohua
AU - Liu, Yongbo
AU - Kim, Sahn Ho
AU - Pindolia, Kirit R.
AU - Arbab, Ali Syed
AU - Gautam, Subhash C.
PY - 2012/6/15
Y1 - 2012/6/15
N2 - 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.
AB - 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.
KW - Akt (protein kinase b)
KW - Apoptosis
KW - CDDO-Me
KW - HTERT
KW - MTS
KW - NF-κB
KW - PARP-1
KW - Pancreatic cancer
KW - STAT-3
KW - Telomerase
UR - http://www.scopus.com/inward/record.url?scp=84862284026&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862284026&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2012.05.024
DO - 10.1016/j.bbrc.2012.05.024
M3 - Article
C2 - 22609405
AN - SCOPUS:84862284026
VL - 422
SP - 561
EP - 567
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -