Acetyl-11-keto-β-boswellic acid suppresses invasion of pancreatic cancer cells through the downregulation of CXCR4 chemokine receptor expression.
Acetyl-11-keto-β-boswellic acid suppresses invasion of pancreatic cancer cells through the downregulation of CXCR4 chemokine receptor expression.
复制标题
DOI：
10.1002/ijc.25966
复制
发表时间：
2011-07-01
影响因子：
6.4
通讯作者：
Aggarwal, Bharat B.
中科院分区：
文献类型：
--
作者：
Park, Byoungduck;Sung, Bokyung;Yadav, Vivek R.;Cho, Sung-Gook;Liu, Mingyao;Aggarwal, Bharat B.
90%的癌症导致的死亡是由于肿瘤的转移，但控制转移的机制仍然知之甚少。因此，目前还没有针对这一过程的治疗方法获得批准。趋化因子及其受体是慢性炎症的介质，与许多癌症的转移有关。最近，CXC趋化因子受体4(CXCR4)已经成为肿瘤转移的关键介质；因此，识别该受体的抑制剂具有消除转移的潜力。在这份报告中，我们证明了治疗植物锯缘博士威的一种成分乙酰基-11-酮-β-博士威酸(AKBA)可以下调胰腺癌细胞中CXCR4的表达。这种萜类化合物诱导的CXCR4的减少被发现是细胞类型特异性的，因为它在白血病、骨髓瘤和乳腺癌细胞系中的表达也被取消。蛋白酶体抑制剂和溶酶体稳定剂都不能阻止AKBA诱导的CXCR4表达下调，下调发生在转录水平。AKBA抑制CXCR4的同时，也抑制了CXCR4的配体CXCL12诱导的胰腺癌细胞侵袭。此外，在原位动物模型中，AKBA还能抑制人胰腺组织趋化因子受体的表达。AKBA还能抑制乳腺肿瘤细胞的侵袭，这种作用与CXCR4mRNA和CXCR4蛋白的消失有关。总体而言，我们的结果表明，AKBA是一种新的CXCR4表达抑制剂，因此具有抑制癌细胞侵袭和转移的潜力。
Ninety percent of cancer-mediated deaths are due to metastasis of the tumor, but the mechanisms controlling metastasis remain poorly understood. Thus, no therapy targeting this process has yet been approved. Chemokines and their receptors are mediators of chronic inflammation and have been linked to the metastasis of numerous cancers. More recently, the CXC chemokine receptor 4 (CXCR4) has emerged as a key mediator of tumor metastasis; therefore, identification of inhibitors of this receptor has the potential to abrogate metastasis. In this report, we demonstrate that acetyl-11-keto-β-boswellic acid (AKBA), a component of the therapeutic plant Boswellia serrata, can downregulate CXCR4 expression in pancreatic cancer cells. The reduction in CXCR4 induced by this terpenoid was found to be cell-type specific, as its expression was also abrogated in leukemia, myeloma, and breast cancer cell lines. Neither proteasome inhibitors nor lysosomal stabilization could prevent the AKBA-induced reduction in CXCR4 expression, and downregulation occurred at the transcriptional level. Suppression of CXCR4 by AKBA was accompanied by the inhibition of pancreatic cancer cell invasion, which is induced by CXCL12, the ligand for CXCR4. In addition, abrogation of the expression of chemokine receptor by AKBA was found in human pancreatic tissues from orthotopic animal model. AKBA also abolished breast tumor cell invasion, and this effect correlated with the disappearance of both the CXCR4 mRNA and CXCR4 protein. Overall, our results show that AKBA is a novel inhibitor of CXCR4 expression and, thus, has the potential to suppress the invasion and metastasis of cancer cells.
登录
查看更多内容
影响因子：
11.2
作者：
Pang X;Yi Z;Zhang X;Sung B;Qu W;Lian X;Aggarwal BB;Liu M
通讯作者：
Liu M
影响因子：
11.2
作者：
Marchesi, F;Monti, P;Allavena, P
通讯作者：
Allavena, P
影响因子：
4.8
作者：
Marchese, A;Benovic, JL
通讯作者：
Benovic, JL
DOI：
10.1084/jem.177.5.1391
发表时间：
1993-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Orosz P;Echtenacher B;Falk W;Rüschoff J;Weber D;Männel DN
通讯作者：
Männel DN
影响因子：
4
作者：
Cabioglu, N;Sahin, A;Price, JE
通讯作者：
Price, JE