Telomerase reverse transcriptase (TERT) is a therapeutic target of oleanane triterpenoid CDDO-Me in prostate cancer.
Telomerase reverse transcriptase (TERT) is a therapeutic target of oleanane triterpenoid CDDO-Me in prostate cancer.
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DOI：
10.3390/molecules171214795
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发表时间：
2012-12-11
期刊：
影响因子：
--
通讯作者：
Gautam SC
中科院分区：
文献类型：
--
作者：
Liu Y;Gao X;Deeb D;Arbab AS;Gautam SC
甲基-2-氰基-3，12-二氧代齐墩果烷-1，9（11）-二烯-28-酸酯（CDDO-Me）是一种人工合成的齐墩果烷三萜类化合物，具有较强的抗肿瘤细胞增殖和促凋亡活性。然而，CDDO-Me对前列腺癌细胞中人端粒酶逆转录酶（hTERT）及其端粒酶活性的影响尚未研究。我们在体外和体内研究了hTERT在介导CDDO-Me在前列腺癌细胞中的抗癌活性中的作用。CDDO-Me抑制LNCaP和PC-3前列腺癌细胞系的细胞增殖和诱导凋亡与抑制hTERT基因表达、hTERT端粒酶活性和许多转录和转录后调节hTERT的蛋白有关。此外，hTERT蛋白的消除增加了癌细胞对CDDO-Me的敏感性，而其过表达使它们对CDDO-Me具有抗性。在TRAMP小鼠中，通过CDDO-Me将低和高级别前列腺上皮内肿瘤（PIN）转化为前列腺腺癌与前列腺中TERT及其调节蛋白的显著降低相关。这些数据提供了证据，端粒酶是CDDO-Me用于预防和治疗前列腺癌的潜在靶点。
Methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me) is an synthetic oleanane triterpenoid with strong antiprolifertive and proapoptotic activities in cancer cells. However, the effect of CDDO-Me on human telomerase reverse transcriptase (hTERT) and its telomerase activity in prostate cancer cells has not been studied. We investigated the role of hTERT in mediating the anticancer activity of CDDO-Me in prostate cancer cells in vitro and in vivo. The inhibition of cell proliferation and induction of apoptosis by CDDO-Me in LNCaP and PC-3 prostate cancer cell lines was associated with the inhibition of hTERT gene expression, hTERT telomerase activity and a number of proteins that regulate hTERT transcriptionally and post-translationally. Furthermore, ablation of hTERT protein increased the sensitivity of cancer cells to CDDO-Me, whereas its overexpression rendered them resistant to CDDO-Me. In addition, inhibition of progression of preneoplastic lesions (i.e., low and high-grade prostate intraepithelial neoplasms, PINs) to adenocarcinoma of the prostate by CDDO-Me in TRAMP mice was associated with significant decrease in TERT and its regulatory proteins in the prostate gland. These data provide evidence that telomerase is a potential target of CDDO-Me for the prevention and treatment of prostate cancer.
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影响因子：
56.9
作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
通讯作者：
VILLEPONTEAU, B
影响因子：
11.2
作者：
Chintharlapalli, Sudhakar;Papineni, Sabitha;Safe, Stephen
通讯作者：
Safe, Stephen
影响因子：
11.2
作者：
Konnikova, L;Simeone, MC;Cochran, BH
通讯作者：
Cochran, BH
影响因子：
4.7
作者：
Deeb, Dorrah;Gao, Xiaohua;Gautam, Subhash C.
通讯作者：
Gautam, Subhash C.
影响因子：
11.4
作者：
Konopleva, M;Contractor, R;Ruvolo, PP
通讯作者：
Ruvolo, PP