Brunie Manon, Robichaud Mika A, Touaibia Mohamed, Martin Luc J
Biology Department, Université de Moncton, Moncton, NB, Canada.
Chemistry and Biochemistry Department, Université de Moncton, Moncton, NB, Canada.
Cell Biochem Biophys. 2025 Jun;83(2):2349-2364. doi: 10.1007/s12013-024-01646-6. Epub 2024 Dec 27.
Targeting more than one in nine men before age 70, prostate cancer is the most common type of cancer in men. The increased levels of cyclins, leading to activation of cyclin-dependent kinases (CDKs), play a critical role in the increased proliferation of prostate cancer cells. In this study, the regulation of the cyclin D1 (CCND1) promoter activity by activator protein-1 (AP-1) and SRY-related HMG-box (SOX) transcription factors has been characterized in PC3 prostate cancer cells. The SOX and AP-1 transcription factors can cooperate to activate the CCND1 promoter in PC3 prostate cancer cells and such cooperation can be enhanced by protein kinase A (PKA) and/or mitogen-activated protein kinase kinase 1 (ERK kinase 1, MAP2K1) signaling pathways. Moreover, anacardic acid analogs have been assessed for their potential in reducing cell viability and CCND1 promoter activity. The anacardic acid analog 8b, obtained from γ-resorcylic acid, reduces the viability and proliferation of PC3 cells by decreasing CCND1 promoter activity. The effect of analog 8b, which perfectly mimics the structure of anacardic acid, can be attributed to the inhibition of the activities of the transcription factors SOX and AP-1, which are important regulators of CCND1 promoter activity in prostate cancer cells.
前列腺癌是男性中最常见的癌症类型，在70岁之前，每九名男性中就有一人以上受其影响。细胞周期蛋白水平的升高会导致细胞周期蛋白依赖性激酶（CDK）的激活，这在前列腺癌细胞增殖增加中起着关键作用。在这项研究中，已在PC3前列腺癌细胞中对激活蛋白-1（AP-1）和SRY相关高迁移率族盒（SOX）转录因子对细胞周期蛋白D1（CCND1）启动子活性的调节进行了表征。SOX和AP-1转录因子可以协同激活PC3前列腺癌细胞中的CCND1启动子，并且这种协同作用可以通过蛋白激酶A（PKA）和/或丝裂原活化蛋白激酶激酶1（ERK激酶1，MAP2K1）信号通路增强。此外，已评估了漆树酸类似物在降低细胞活力和CCND1启动子活性方面的潜力。从γ-间苯二酚获得的漆树酸类似物8b通过降低CCND1启动子活性来降低PC3细胞的活力和增殖。类似物8b完美模拟漆树酸的结构，其作用可归因于对转录因子SOX和AP-1活性的抑制，而这两种转录因子是前列腺癌细胞中CCND1启动子活性的重要调节因子。
