NBM-T-BBX-OS01, Semisynthesized from Osthole, Induced G1 Growth Arrest through HDAC6 Inhibition in Lung Cancer Cells.
NBM-T-BBX-OS01, Semisynthesized from Osthole, Induced G1 Growth Arrest through HDAC6 Inhibition in Lung Cancer Cells.
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DOI：
10.3390/molecules20058000
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发表时间：
2015-05-04
期刊：
影响因子：
--
通讯作者：
Weng MS
中科院分区：
文献类型：
--
作者：
Pai JT;Hsu CY;Hua KT;Yu SY;Huang CY;Chen CN;Liao CH;Weng MS
通过抑制组蛋白去乙酰化酶（hdac）来破坏肺肿瘤的生长是一种治疗或预防癌症的策略。靶向HDAC6可能会干扰热休克蛋白90 （Hsp90）介导的细胞周期调控。在这项研究中，我们证明了从蛇床子中提取的半合成NBM-T-BBX-OS01 （TBBX）对hdac6介导的肺癌细胞生长阻滞的影响。结果显示，TBBX在多种肺癌细胞中的抗增殖活性比临床批准的泛hdac抑制剂亚eroylanilide hydroxamic acid （SAHA）更强，其生长抑制作用是通过G1期生长阻滞介导的。此外，在tbbx处理的H1299细胞中，cyclin D1、CDK2和CDK4的蛋白水平降低，而cyclin E和CDK抑制剂p21Waf1/Cip1的蛋白水平上调。结果还表明，TBBX通过下调HDAC6蛋白表达抑制HDAC6活性。TBBX诱导Hsp90超乙酰化，通过蛋白酶体降解cyclin D1和CDK4蛋白，导致cyclin D1/Hsp90和CDK4/Hsp90的关联被破坏。H1299细胞中HDAC6异位表达挽救tbbx诱导的G1阻滞。总之，这些数据表明，TBBX诱导的G1生长停滞可能介导hdac6引起的Hsp90超乙酰化，从而增加cyclin D1和CDK4的降解。
Disrupting lung tumor growth via histone deacetylases (HDACs) inhibition is a strategy for cancer therapy or prevention. Targeting HDAC6 may disturb the maturation of heat shock protein 90 (Hsp90) mediated cell cycle regulation. In this study, we demonstrated the effects of semisynthesized NBM-T-BBX-OS01 (TBBX) from osthole on HDAC6-mediated growth arrest in lung cancer cells. The results exhibited that the anti-proliferative activity of TBBX in numerous lung cancer cells was more potent than suberoylanilide hydroxamic acid (SAHA), a clinically approved pan-HDAC inhibitor, and the growth inhibitory effect has been mediated through G1 growth arrest. Furthermore, the protein levels of cyclin D1, CDK2 and CDK4 were reduced while cyclin E and CDK inhibitor, p21Waf1/Cip1, were up-regulated in TBBX-treated H1299 cells. The results also displayed that TBBX inhibited HDAC6 activity via down-regulation HDAC6 protein expression. TBBX induced Hsp90 hyper-acetylation and led to the disruption of cyclin D1/Hsp90 and CDK4/Hsp90 association following the degradation of cyclin D1 and CDK4 proteins through proteasome. Ectopic expression of HDAC6 rescued TBBX-induced G1 arrest in H1299 cells. Conclusively, the data suggested that TBBX induced G1 growth arrest may mediate HDAC6-caused Hsp90 hyper-acetylation and consequently increased the degradation of cyclin D1 and CDK4.
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影响因子：
--
作者：
Aldana-Masangkay GI;Sakamoto KM
通讯作者：
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影响因子：
64.8
作者：
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影响因子：
11.5
作者：
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作者：
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通讯作者：
Canepa, Eduardo T.
DOI：
10.1016/j.bbrc.2008.06.092
发表时间：
2008-09-12
影响因子：
3.1
作者：
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