Molecular signatures of sanguinarine in human pancreatic cancer cells: A large scale label-free comparative proteomics approach.
Molecular signatures of sanguinarine in human pancreatic cancer cells: A large scale label-free comparative proteomics approach.
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DOI：
10.18632/oncotarget.3231
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发表时间：
2015-04-30
期刊：
影响因子：
--
通讯作者：
Ahmad N
中科院分区：
文献类型：
--
作者：
Singh CK;Kaur S;George J;Nihal M;Pellitteri Hahn MC;Scarlett CO;Ahmad N
胰腺癌仍然是人类所有恶性肿瘤中最致命的一种，其发病率几乎与死亡率持平。因此，寻找新的基于机制的药物和靶点来有效地管理胰腺癌是至关重要的。植物衍生剂/药物历来在癌症治疗中很有用。血根碱是一种植物生物碱，具有抗肿瘤增殖的作用，包括胰腺癌。本研究旨在确定血根碱在胰腺癌中的作用机制，以期获得有用的信息，以改善胰腺癌的治疗选择。我们使用定量蛋白质组学的方法来确定血根碱对人胰腺癌细胞的作用机制。用胰酶消化对照和血根素处理的胰腺癌细胞的蛋白质，经Nano-LC/MS/MS运行，并借助Swiss-PROT数据库进行鉴定。重复注射的结果用Sieve软件处理，以鉴定差异表达的蛋白质。我们鉴定了37个差异表达的蛋白质(总共3107个)，它们已知参与了各种细胞过程。其中4个蛋白(IL33、CUL5、GPS1和DUSP4)似乎占据了关键通路的调控节点。进一步的QRT-PCR和免疫印迹分析表明，血根素显著上调BxPC-3和MIA Paca-2细胞的双特异性磷酸酶-4(DUSP4)。血根碱治疗还导致HIF1α和增殖细胞核抗原表达下调，PARP和Caspase-7裂解增加。综上所述，血根碱似乎具有多效性作用，因为它调节多个关键信号通路，支持血根碱对胰腺癌的潜在有效性。
Pancreatic cancer remains one of the most lethal of all human malignancies with its incidence nearly equaling its mortality rate. Therefore, it's crucial to identify newer mechanism-based agents and targets to effectively manage pancreatic cancer. Plant-derived agents/drugs have historically been useful in cancer therapeutics. Sanguinarine is a plant alkaloid with anti-proliferative effects against cancers, including pancreatic cancer. This study was designed to determine the mechanism of sanguinarine's effects in pancreatic cancer with a hope to obtain useful information to improve the therapeutic options for the management of this neoplasm. We employed a quantitative proteomics approach to define the mechanism of sanguinarine's effects in human pancreatic cancer cells. Proteins from control and sanguinarine-treated pancreatic cancer cells were digested with trypsin, run by nano-LC/MS/MS, and identified with the help of Swiss-Prot database. Results from replicate injections were processed with the SIEVE software to identify proteins with differential expression. We identified 37 differentially expressed proteins (from a total of 3107), which are known to be involved in variety of cellular processes. Four of these proteins (IL33, CUL5, GPS1 and DUSP4) appear to occupy regulatory nodes in key pathways. Further validation by qRT-PCR and immunoblot analyses demonstrated that the dual specificity phosphatase-4 (DUSP4) was significantly upregulated by sanguinarine in BxPC-3 and MIA PaCa-2 cells. Sanguinarine treatment also caused down-regulation of HIF1α and PCNA, and increased cleavage of PARP and Caspase-7. Taken together, sanguinarine appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of sanguinarine against pancreatic cancer.
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影响因子：
2.9
作者：
Deer EL;González-Hernández J;Coursen JD;Shea JE;Ngatia J;Scaife CL;Firpo MA;Mulvihill SJ
通讯作者：
Mulvihill SJ
影响因子：
37.3
作者：
Fay MJ;Longo KA;Karathanasis GA;Shope DM;Mandernach CJ;Leong JR;Hicks A;Pherson K;Husain A
通讯作者：
Husain A
DOI：
10.1016/j.bbrc.2004.03.077
发表时间：
2004-04-30
影响因子：
3.1
作者：
Eun, JP;Koh, GY
通讯作者：
Koh, GY
影响因子：
37.3
作者：
Duffy JP;Eibl G;Reber HA;Hines OJ
通讯作者：
Hines OJ
影响因子：
8
作者：
Cagnol, S.;Rivard, N.
通讯作者：
Rivard, N.