Characterization of PPAR dual ligand MCC-555 in AOM-induced colorectal tumorigenesis.
Characterization of PPAR dual ligand MCC-555 in AOM-induced colorectal tumorigenesis.
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DOI：
10.1016/j.etp.2013.01.005
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Baek SJ
中科院分区：
文献类型：
--
作者：
Imchen T;Manasse J;Min KW;Baek SJ
结直肠癌（CRC）是最常见的诊断癌症之一。过氧化物酶体增殖物激活受体γ（过氧化物酶体增殖物激活受体γ，PPARγ）激动剂通过影响细胞增殖、分化和凋亡而代表用于癌症治疗的潜在重要的化学预防/治疗化合物家族。已开发出PPARα和PPARγ的双配体，如奈格列酮（MCC-555），用于改善代谢综合征（包括高血糖症和高脂血症）的治疗。有趣的是，这些双重配体还具有针对多种癌细胞系的抗增殖活性，其效力大于常规的PPARγ特异性配体。在这项研究中，使用氧化偶氮甲烷（AOM）诱导的A/J小鼠结肠异常隐窝灶（ACF）评价MCC-555在结直肠肿瘤发生中的化学预防特性。我们发现，与对照组相比，MCC-555抑制A/J小鼠中AOM诱导的ACF。MCC-555给药导致结肠中有丝分裂减少和凋亡细胞增加。此外，肿瘤抑制蛋白MUC 2的表达在MCC-555处理的小鼠中增加。我们的数据清楚地表明，MCC-555对结肠癌发生的早期事件有影响，从而提供了MCC-555可能是CRC的潜在预防化合物的证据。
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers. Peroxisome proliferator-activated receptor γ (PPARγ) agonists represent a potentially important family of chemopreventive/therapeutic compounds for cancer treatment by affecting cell proliferation, differentiation, and apoptosis. Dual ligands for PPARα and PPARγ, such as netoglitazone (MCC-555), have been developed to improve treatment of metabolic syndromes, including hyperglycemia and hyperlipidemia. Interestingly, these dual ligands also possess anti-proliferative activities against a variety of cancer cell lines with a greater potency than conventional PPARγ specific ligands. In this study, chemopreventive properties of MCC-555 in colorectal tumorigenesis were evaluated using azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in A/J mice. We found that MCC-555 suppressed AOM-induced ACF in A/J mice, compared to the control group. Administration of MCC-555 resulted in decreased mitoses and increased apoptotic cells in the colon. Furthermore, expression of tumor suppressor protein MUC2 was increased in MCC-555 treated mice. Our data clearly suggest that MCC-555 has an effect on the early events of colon carcinogenesis, thus providing evidence that MCC-555 could be a potential preventive compound for CRC.
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DOI：
10.1073/pnas.95.15.8806
发表时间：
1998-07-21
影响因子：
11.1
作者：
Elstner, E;Müller, C;Koeffler, HP
通讯作者：
Koeffler, HP
DOI：
10.1083/jcb.200311021
发表时间：
2004-07-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Jay P
影响因子：
5.7
作者：
Chintharlapalli, Sudhakar;Papineni, Sabitha;Safe, Stephen
通讯作者：
Safe, Stephen
影响因子：
2.1
作者：
Rumi, MAK;Ishihara, S;Kinoshita, Y
通讯作者：
Kinoshita, Y
影响因子：
6.4
作者：
Kohno, Hiroyuki;Suzuki, Rikako;Tanaka, Takuji
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Tanaka, Takuji