Curcumin Suppresses Human Papillomavirus Oncoproteins, Restores p53, Rb, and PTPN13 Proteins and Inhibits Benzo[a]pyrene-Induced Upregulation of HPV E7
Curcumin Suppresses Human Papillomavirus Oncoproteins, Restores p53, Rb, and PTPN13 Proteins and Inhibits Benzo[a]pyrene-Induced Upregulation of HPV E7
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DOI：
10.1002/mc.20695
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发表时间：
2011-01-01
影响因子：
4.6
通讯作者：
Chauhan, Subhash C.
中科院分区：
文献类型：
--
作者：
Maher, Diane M.;Bell, Maria C.;Chauhan, Subhash C.
姜黄素作为化学预防和化学治疗剂具有很大的潜力，然而，其对人乳头瘤病毒（HPV）相关分子事件的影响还没有充分探讨。这项研究检查了姜黄素对HPV相关通路的影响，这些通路参与宫颈癌的发展。我们首次证明姜黄素治疗抑制宫颈癌细胞在三维筏培养系统中的生长。姜黄素还抑制肿瘤发生的特性，如克隆形成潜力和细胞运动性的降低所示。此外，我们的研究结果表明，姜黄素治疗早在治疗后6小时就抑制了HPV 16 E6/E7的转录，并恢复了肿瘤抑制蛋白p53、视网膜母细胞瘤蛋白和PTPN 13的表达。虽然吸烟是宫颈癌的公认危险因素，但吸烟致癌物对HPV E6/E7癌基因表达的分子影响尚不清楚。我们首次表明，暴露于苯并[a]芘（BaP），烟草致癌物，增加HPV E7癌蛋白的表达，表明吸烟和宫颈癌之间的分子联系。重要的是，姜黄素降低了BaP诱导的HPV E7癌蛋白表达的增加。这项研究的结果清楚地表明，姜黄素改变了宫颈癌细胞中HPV相关的分子途径。这些新的发现意味着姜黄素可能是一种有效的预防和治疗宫颈癌的化学预防和治疗剂。(C)2010 Wiley-Liss，Inc.
Curcumin has great potential as a chemopreventive and chemotherapeutic agent; however, its effects on human papillomavirus (HPV)-associated molecular events are inadequately explored. This study examined the effects of curcumin on HPV-associated pathways involved in developing cervical cancer. We demonstrate for the first time that curcumin treatment suppresses cervical cancer cell growth in a three-dimensional raft culture system. Curcumin also inhibits tumorigenic characteristics as shown by decreases in both clonogenic potential and cell motility. Additionally, our findings show that curcumin treatment inhibits the transcription of HPV16 E6/E7 as early as 6 h posttreatment and restores the expression of tumor suppressor proteins p53, retinoblastoma protein, and PTPN13. While smoking is a recognized risk factor for cervical cancer, the molecular effects of smoke carcinogens on the expression of HPV E6/E7 oncogenes are not well known. We show for the first time that exposure to benzo[a] pyrene (BaP), a tobacco carcinogen, increases the expression of HPV E7 oncoprotein suggesting a molecular link between smoking and cervical cancer. Importantly, curcumin decreases the BaP induced increase in the expression of HPV E7 oncoprotein. The results of this study clearly demonstrate that curcumin alters HPV-associated molecular pathways in cervical cancer cells. These novel findings imply that curcumin may be an effective chemopreventive and therapeutic agent for cervical cancer prevention and treatment. (C) 2010 Wiley-Liss, Inc.