齐墩果酸三萜（CDDO-Me）通过抑制端粒酶逆转录酶基因表达及其端粒酶活性抑制胰腺癌细胞增殖并诱导其凋亡。
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.
机构信息
Department of Surgery, Henry Ford Health System, Detroit, MI 48202, USA.
出版信息
Biochem Biophys Res Commun. 2012 Jun 15;422(4):561-7. doi: 10.1016/j.bbrc.2012.05.024. Epub 2012 May 16.
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.
摘要
2-氰基-3,12-二氧代齐墩果-1,9(11)-二烯-28-酸甲酯（CDDO-Me）是一种具有强大抗炎和抗肿瘤特性的多功能齐墩果烷合成三萜。CDDO-Me 和相关的齐墩果酸衍生物的抗生存和诱导凋亡活性的机制已经确定；然而，迄今为止，尚未有关于 CDDO 对人端粒酶逆转录酶（hTERT）基因或端粒酶活性的影响的研究。在这里，我们首次报道 CDDO-Me 在胰腺癌细胞系中抑制细胞增殖和诱导细胞凋亡与抑制 hTERT 基因表达、hTERT 端粒酶活性以及调节 hTERT 表达和活性的多种蛋白质有关。此外，hTERT 蛋白的缺失或过表达改变了肿瘤细胞对 CDDO-Me 的敏感性。这些发现表明，端粒酶（hTERT）是 CDDO-Me 在胰腺癌细胞中的一个相关靶点。
相似文献
1
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.齐墩果酸三萜（CDDO-Me）通过抑制端粒酶逆转录酶基因表达及其端粒酶活性抑制胰腺癌细胞增殖并诱导其凋亡。
Biochem Biophys Res Commun. 2012 Jun 15;422(4):561-7. doi: 10.1016/j.bbrc.2012.05.024. Epub 2012 May 16.
2
Inhibition of telomerase activity by oleanane triterpenoid CDDO-Me in pancreatic cancer cells is ROS-dependent.齐墩果烷三萜 CDDO-Me 通过 ROS 依赖途径抑制胰腺癌细胞端粒酶活性。
Molecules. 2013 Mar 13;18(3):3250-65. doi: 10.3390/molecules18033250.
3
Telomerase reverse transcriptase (TERT) is a therapeutic target of oleanane triterpenoid CDDO-Me in prostate cancer.端粒酶逆转录酶（TERT）是齐墩果酸三萜 CDDO-Me 在前列腺癌中的治疗靶点。
Molecules. 2012 Dec 11;17(12):14795-809. doi: 10.3390/molecules171214795.
4
Induction of Apoptosis in Pancreatic Cancer Cells by CDDO-Me Involves Repression of Telomerase through Epigenetic Pathways.CDDO-Me诱导胰腺癌细胞凋亡涉及通过表观遗传途径抑制端粒酶。
J Carcinog Mutagen. 2014 May 31;5:177. doi: 10.4172/2157-2518.1000177.
5
6
Oleanane triterpenoid CDDO-Me inhibits growth and induces apoptosis in prostate cancer cells by independently targeting pro-survival Akt and mTOR.齐墩果烷三萜类化合物CDDO-Me通过独立靶向促生存的Akt和mTOR来抑制前列腺癌细胞的生长并诱导其凋亡。
Prostate. 2009 Jun 1;69(8):851-60. doi: 10.1002/pros.20937.
7
8
c-FLIP downregulation contributes to apoptosis induction by the novel synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9-dien-28-oate (CDDO-Me) in human lung cancer cells.c-FLIP下调有助于新型合成三萜类化合物甲基-2-氰基-3,12-二氧代齐墩果-1,9-二烯-28-酸酯（CDDO-Me）诱导人肺癌细胞凋亡。
Cancer Biol Ther. 2007 Oct;6(10):1614-20. doi: 10.4161/cbt.6.10.4763. Epub 2007 Jul 19.
9
Synthetic triterpenoids inhibit growth and induce apoptosis in human glioblastoma and neuroblastoma cells through inhibition of prosurvival Akt, NF-kappaB and Notch1 signaling.合成三萜类化合物通过抑制促生存的Akt、核因子κB和Notch1信号传导，抑制人胶质母细胞瘤和神经母细胞瘤细胞的生长并诱导其凋亡。
J Neurooncol. 2007 Sep;84(2):147-57. doi: 10.1007/s11060-007-9364-9. Epub 2007 Mar 15.
引用本文的文献
1
Bardoxolone Methyl: A Comprehensive Review of Its Role as a Nrf2 Activator in Anticancer Therapeutic Applications.甲基巴多索隆：对其作为Nrf2激活剂在抗癌治疗应用中的作用的全面综述。
Pharmaceuticals (Basel). 2025 Jun 27;18(7):966. doi: 10.3390/ph18070966.
2
Pristimerin Promotes Ubiquitination of HSPA8 and Activates the VAV1/ERK Pathway to Suppress TNBC Proliferation.扁蒴藤素促进HSPA8的泛素化并激活VAV1/ERK通路以抑制三阴性乳腺癌的增殖。
Adv Sci (Weinh). 2025 Mar;12(10):e2413174. doi: 10.1002/advs.202413174. Epub 2025 Jan 15.
3
Anti-Cancer Effects of Pristimerin and the Mechanisms: A Critical Review.鸦胆子素的抗癌作用及其机制：一项批判性综述
Front Pharmacol. 2019 Jul 12;10:746. doi: 10.3389/fphar.2019.00746. eCollection 2019.
4
Telomerase Inhibitors from Natural Products and Their Anticancer Potential.天然产物来源的端粒酶抑制剂及其抗癌潜力。
Int J Mol Sci. 2017 Dec 21;19(1):13. doi: 10.3390/ijms19010013.
5
Time Course Expression Analysis of 1[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole Induction of Cytoprotection in Human Endothelial Cells.1-[2-氰基-3,12-二氧代齐墩果-1,9(11)-二烯-28-酰基]咪唑诱导人内皮细胞产生细胞保护作用的时间进程表达分析
Gene Regul Syst Bio. 2017 Apr 7;11:1177625017701106. doi: 10.1177/1177625017701106. eCollection 2017.
6
Aphanin, a triterpenoid from Amoora rohituka inhibits K-Ras mutant activity and STAT3 in pancreatic carcinoma cells.阿帕宁，一种从绒毛山竹子中提取的三萜类化合物，可抑制胰腺癌细胞中的K-Ras突变体活性和信号转导与转录激活因子3（STAT3）。
Tumour Biol. 2016 Sep;37(9):12455-12464. doi: 10.1007/s13277-016-5102-2. Epub 2016 Jun 22.
7
Hsp90 Is a Novel Target Molecule of CDDO-Me in Inhibiting Proliferation of Ovarian Cancer Cells.热休克蛋白90是CDDO-Me抑制卵巢癌细胞增殖的新型靶分子。
PLoS One. 2015 Jul 2;10(7):e0132337. doi: 10.1371/journal.pone.0132337. eCollection 2015.
8
Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition.人类癌症中的基因组不稳定性：分子见解以及通过饮食和营养进行治疗性攻击和预防的机会。
Semin Cancer Biol. 2015 Dec;35 Suppl(Suppl):S5-S24. doi: 10.1016/j.semcancer.2015.03.005. Epub 2015 Apr 11.
9
Downregulation of telomerase activity by diclofenac and curcumin is associated with cell cycle arrest and induction of apoptosis in colon cancer.双氯芬酸和姜黄素对端粒酶活性的下调与结肠癌中的细胞周期停滞及细胞凋亡诱导相关。
Tumour Biol. 2015 Aug;36(8):5999-6010. doi: 10.1007/s13277-015-3276-7. Epub 2015 Mar 6.
10
Dose-dependent cytotoxic effects of boldine in HepG-2 cells-telomerase inhibition and apoptosis induction.波尔定碱在HepG-2细胞中的剂量依赖性细胞毒性作用——端粒酶抑制与凋亡诱导
Molecules. 2015 Feb 24;20(3):3730-43. doi: 10.3390/molecules20033730.
本文引用的文献
1
Oleanane triterpenoid CDDO-Me inhibits Akt activity without affecting PDK1 kinase or PP2A phosphatase activity in cancer cells.齐墩果烷三萜 CDDO-Me 可抑制肿瘤细胞中的 Akt 活性，而不影响 PDK1 激酶或 PP2A 磷酸酶的活性。
Biochem Biophys Res Commun. 2012 Jan 6;417(1):570-5. doi: 10.1016/j.bbrc.2011.12.007. Epub 2011 Dec 8.
2
Prevention of Prostate Cancer with Oleanane Synthetic Triterpenoid CDDO-Me in the TRAMP Mouse Model of Prostate Cancer.用齐墩果烷型三萜烯 CDDO-Me 预防前列腺癌（TRAMP 小鼠前列腺癌模型）
Cancers (Basel). 2011;3(3):3353-69. doi: 10.3390/cancers3033353.
3
Synthetic triterpenoid CDDO prevents the progression and metastasis of prostate cancer in TRAMP mice by inhibiting survival signaling.合成三萜类化合物 CDDO 通过抑制存活信号转导预防 TRAMP 小鼠前列腺癌的进展和转移。
Carcinogenesis. 2011 May;32(5):757-64. doi: 10.1093/carcin/bgr030. Epub 2011 Feb 16.
4
Synthetic triterpenoids prolong survival in a transgenic mouse model of pancreatic cancer.合成三萜延长胰腺癌转基因小鼠模型的生存期。
Cancer Prev Res (Phila). 2010 Nov;3(11):1427-34. doi: 10.1158/1940-6207.CAPR-10-0197. Epub 2010 Oct 19.
5
Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines.萝卜硫素导致人类乳腺癌细胞系中端粒酶逆转录酶表达的表观遗传抑制。
PLoS One. 2010 Jul 6;5(7):e11457. doi: 10.1371/journal.pone.0011457.
6
Genistein depletes telomerase activity through cross-talk between genetic and epigenetic mechanisms.金雀异黄素通过遗传和表观遗传机制之间的相互作用降低端粒酶活性。
Int J Cancer. 2009 Jul 15;125(2):286-96. doi: 10.1002/ijc.24398.
7
Novel semisynthetic triterpenoid AMR-Me inhibits telomerase activity in human leukemic CEM cells and exhibits in vivo antitumor activity against Dalton's lymphoma ascites tumor.新型半合成三萜类化合物AMR-Me抑制人白血病CEM细胞中的端粒酶活性，并对道尔顿淋巴瘤腹水瘤表现出体内抗肿瘤活性。
Cancer Lett. 2009 Jun 18;278(2):156-163. doi: 10.1016/j.canlet.2009.01.003. Epub 2009 Feb 6.
8
Telomere-associated proteins: cross-talk between telomere maintenance and telomere-lengthening mechanisms.端粒相关蛋白：端粒维持与端粒延长机制之间的相互作用
J Pathol. 2009 Feb;217(3):327-44. doi: 10.1002/path.2500.
9
The novel triterpenoid C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid inhibits metastatic murine breast tumor growth through inactivation of STAT3 signaling.新型三萜类化合物2-氰基-3,12-二氧代齐墩果-1,9-二烯-28-酸C-28甲酯通过使信号转导和转录激活因子3（STAT3）信号失活来抑制转移性小鼠乳腺肿瘤生长。
Cancer Res. 2007 May 1;67(9):4210-8. doi: 10.1158/0008-5472.CAN-06-3629.
10
Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer.三萜类化合物和视黄酸类化合物作为预防和治疗癌症的多功能药物。
Nat Rev Cancer. 2007 May;7(5):357-69. doi: 10.1038/nrc2129. Epub 2007 Apr 19.
Zotero 插件