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

Dorrah Deeb; Xiaohua Gao; Yongbo Liu; Sahn Ho Kim; Kirit R. Pindolia; Ali S. Arbab; Subhash C. Gautam

doi:10.1016/j.bbrc.2012.05.024

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

Dorrah Deeb, Xiaohua Gao, Yongbo Liu, Sahn Ho Kim, Kirit R. Pindolia, Ali S. Arbab, Subhash C. Gautam

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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	https://doi.org/10.1016/j.bbrc.2012.05.024
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

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Deeb, D., Gao, X., Liu, Y., Kim, S. H., Pindolia, K. R., Arbab, A. S., & Gautam, S. C. (2012). 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. Biochemical and Biophysical Research Communications, 422(4), 561-567. https://doi.org/10.1016/j.bbrc.2012.05.024

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 S.; 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 › peer-review

Deeb, D, Gao, X, Liu, Y, Kim, SH, Pindolia, KR, Arbab, AS & Gautam, SC 2012, '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', Biochemical and Biophysical Research Communications, vol. 422, no. 4, pp. 561-567. https://doi.org/10.1016/j.bbrc.2012.05.024

Deeb D, Gao X, Liu Y, Kim SH, Pindolia KR, Arbab AS et al. 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. Biochemical and Biophysical Research Communications. 2012 Jun 15;422(4):561-567. https://doi.org/10.1016/j.bbrc.2012.05.024

Deeb, Dorrah ; Gao, Xiaohua ; Liu, Yongbo ; Kim, Sahn Ho ; Pindolia, Kirit R. ; Arbab, Ali S. ; Gautam, Subhash C. / 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. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 422, No. 4. pp. 561-567.

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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.",

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AU - Arbab, Ali S.

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