Jeon Young-Joo, Bang Woong, Choi Yung Hyun, Shim Jung-Hyun, Chae Jung-Il
Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University.
Biol Pharm Bull. 2015;38(9):1302-8. doi: 10.1248/bpb.b15-00159.
Lung cancer is the leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) is the most common pathological type with a reported frequency of about 85% of all cases. Despite recent advances in therapeutic agents and targeted therapies, the prognosis for NSCLC remains poor, and therefore it is important to identify the biological targets of this complex disease since a blockade of such targets would affect multiple downstream signaling cascades. β-Lapachone (β-Lap) is an antiproliferative agent that selectively induces apoptosis-related cell death in a variety of human cancer cells. However, the mechanisms of its action require further investigation. In this study, we show that treatment with β-lap triggers apoptosis and cell-cycle arrest in two NSCLC cell lines: H1299 and NCI-H358. The transcription factor specificity protein 1 (Sp1) was markedly inhibited by β-lap in a dose- and time-dependent manner. Furthermore, β-lap modulated the protein expression levels of the Sp1 regulatory genes, including cell-cycle regulatory proteins and antiapoptotic proteins, resulting in apoptosis. Taken together, our results indicate that β-lap may be a potential antiproliferative agent candidate by inducing apoptotic cell death in NSCLC tissue through downregulation of Sp1.
肺癌是全球癌症相关死亡的主要原因，非小细胞肺癌（NSCLC）是最常见的病理类型，报告显示其在所有病例中的发生率约为85%。尽管治疗药物和靶向治疗最近取得了进展，但NSCLC的预后仍然很差，因此，识别这种复杂疾病的生物学靶点很重要，因为阻断这些靶点会影响多个下游信号级联反应。β-拉帕醌（β-Lap）是一种抗增殖剂，可在多种人类癌细胞中选择性诱导凋亡相关的细胞死亡。然而，其作用机制需要进一步研究。在本研究中，我们表明用β-拉帕醌处理会在两种NSCLC细胞系（H1299和NCI-H358）中引发凋亡和细胞周期停滞。转录因子特异性蛋白1（Sp1）被β-拉帕醌以剂量和时间依赖性方式显著抑制。此外，β-拉帕醌调节Sp1调控基因的蛋白表达水平，包括细胞周期调控蛋白和抗凋亡蛋白，从而导致凋亡。综上所述，我们的结果表明，β-拉帕醌可能是一种潜在的抗增殖剂候选物，通过下调Sp1在NSCLC组织中诱导凋亡性细胞死亡。
