New potential anti-cancer agents synergize with bortezomib and ABT-737 against prostate cancer.
New potential anti-cancer agents synergize with bortezomib and ABT-737 against prostate cancer.
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新的潜在抗癌药物与前列腺癌协同和ABT-737协同作用。
DOI：
10.1002/pros.21116
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发表时间：
2010-06-01
期刊：
影响因子：
--
通讯作者：
Gartel AL
中科院分区：
文献类型：
--
作者：
Pandit B;Gartel AL
我们先前描述了一种转录抑制剂ARC和FoxM 1抑制剂，Siomycin A和thiostrepton的鉴定，它们能够在不同来源的癌细胞系中诱导有效的p53非依赖性细胞凋亡。在这里，我们报告了这些药物对前列腺癌细胞系的表征。我们发现，ARC抑制前列腺癌细胞的活力，并在低纳摩尔浓度诱导凋亡。它有效地下调Mcl-1的表达，并与Bcl-2抑制剂ABT-737显示出协同作用。噻唑类抗生素、硅霉素A和硫链丝菌素在低微摩尔浓度下抑制前列腺癌细胞的生长并诱导细胞死亡。Siomycin A和thiostrepton对致癌转录因子FoxM 1的抑制与诱导细胞凋亡相关。此外，在与蛋白酶体抑制剂硼替佐米联合治疗后，硫链丝菌素和ARC协同诱导前列腺癌细胞凋亡。此外，我们发现，所有测试的药物组合能够选择性地诱导细胞凋亡的转化，但不是正常细胞的相同来源。总体而言，这些化合物代表了治疗前列腺癌药物开发的潜在候选药物。
We previously described the identification of a transcriptional inhibitor ARC and FoxM1 inhibitors, Siomycin A and thiostrepton that were able to induce potent p53-independent apoptosis in cancer cell lines of different origin. Here, we report the characterization of these drugs on a panel of prostate cancer cell lines. We showed that ARC inhibited the viability of prostate cancer cells and induced apoptosis in low nanomolar concentration. It potently downregulated the expression of Mcl-1 and showed synergistic combination effect with Bcl-2 inhibitor ABT-737. Thiazole antibiotics, Siomycin A and thiostrepton inhibited growth and induced cell death in prostate cancer cells in low micromolar concentrations. The inhibition of the oncogenic transcription factor FoxM1 by Siomycin A and thiostrepton correlated with the induction of apoptosis. In addition, thiostrepton and ARC synergistically induced apoptosis in prostate cancer cells following combination treatment with proteasome inhibitor bortezomib. Furthermore, we found that all tested drug combinations were able to induce apoptosis selectively in transformed, but not normal cells of the same origin. Overall, these compounds represent potential candidates for drug development against prostate cancer.
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前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
影响因子：
3.8
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
通讯作者：
Monzon, Federico A.
影响因子：
6.4
作者：
Bhat, Uppoor G.;Gartel, Andrei L.
通讯作者：
Gartel, Andrei L.
影响因子：
8
作者：
Adams, J;Elliott, PJ
通讯作者：
Elliott, PJ
影响因子：
8
作者：
Radhakrishnan, S. K.;Bhat, U. G.;Gartel, A. L.
通讯作者：
Gartel, A. L.
影响因子：
8
作者：
Radhakrishnan, S. K.;Halasi, M.;Gartel, A. L.
通讯作者：
Gartel, A. L.