Downregulation of Sp1 is involved in honokiol-induced cell cycle arrest and apoptosis in human malignant pleural mesothelioma cells
Downregulation of Sp1 is involved in honokiol-induced cell cycle arrest and apoptosis in human malignant pleural mesothelioma cells
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DOI：
10.3892/or.2013.2353
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发表时间：
2013-06-01
期刊：
影响因子：
4.2
通讯作者：
Shim, Jung-Hyun
中科院分区：
文献类型：
--
作者：
Chae, Jung-Il;Jeon, Young-Joo;Shim, Jung-Hyun
恶性胸膜间皮瘤（MPM）是一种极具侵袭性的癌症类型，由于其快速进展，与患者预后不良相关。新的治疗药物，如honoklastine（HNK）改善癌症治疗的临床结果，但所涉及的机制尚未完全阐明。本研究旨在观察HNK对MSTO-211 H间皮瘤细胞生长和凋亡的调控作用，并探讨其抗癌机制。结果显示，HNK能显著降低MSTO-211 H细胞的存活率，增加亚G（1）细胞群，抑制特异性蛋白1（Sp1）的表达。HNK可降低Sp1调节蛋白的转录活性，包括cyclin D1、Mcl-1和survivin，从而通过增加Bax、降低Bid和Bcl-xL以及激活caspase-3和PARP诱导间皮瘤细胞凋亡。结果提示，Sp1作为HNK的一个新的分子靶点，可能通过调节MPM中的信号转导通路而参与细胞周期阻滞和诱导凋亡。
Malignant pleural mesothelioma (MPM) is an extremely aggressive type of cancer and is associated with a poor patient prognosis due to its rapid progression. Novel therapeutic agents such as honokiol (HNK) improve the clinical outcomes of cancer therapy, yet the mechanisms involved have not been fully elucidated. The present study examined the regulatory effects of HNK on the growth and apoptosis of MSTO-211H mesothelioma cells and investigated its anticancer mechanism. The results revealed that HNK significantly reduced the cell viability and increased the sub-G(1) population in MSTO-211H cells and suppressed the expression of the specificity protein 1 protein (Sp1). HNK reduced the transcriptional activity of Sp1 regulatory proteins, including cyclin D1, Mcl-1 and survivin, and, thus, induced apoptosis signaling pathways by increasing Bax, reducing Bid and Bcl-xL and activating caspase-3 and PARP in mesothelioma cells. The results suggest that Sp1, a novel molecular target of HNK, may be related to cell cycle arrest and apoptosis induction through the modulation of signal transduction pathways in MPM.