Sun Yangyan, Wang Min, Ling Jing, Wu Qunying, Han Guorong, Zhou Junxu
Department of Gynecology, Jiangyin Hospital Affiliated to Nantong University, Wuxi, 214400, Jiangsu, People's Republic of China.
Department of Gynecology, Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, 214000, Jiangsu, People's Republic of China.
Hum Cell. 2024 Dec 24;38(1):35. doi: 10.1007/s13577-024-01164-w.
Curzerenone is a major component of the traditional herbal medicine Curcumae Rhizoma with potential cancer-suppressing effects. This study aims to investigate the treatment effect of Curzerenone on cervical cancer cells and the underpinning mechanism. HeLa and SiHa cells were treated with Curzerenone. The 100 μM Curzerenone treatment repressed proliferation, migration, and invasion of the cells. The Curzerenone treatment also reduced cellular expression of programmed death ligand 1, which increased the proliferation and activity of CD8 T cells in a co-culture system with cancer cells. Casein kinase 2 beta (CSNK2B), a predicted physiological target of Curzerenone, was found to be suppressed by Curzerenone. Further overexpression of CSNK2B blocked the treatment effects of Curzerenone. Curzerenone inhibited while CSNK2B triggered activation of the nuclear factor-kappa B (NF-κB) pathway. The oncogenic and immunosuppressive effects of CSNK2B were blocked by an NF-κB-specific inhibitor. In vivo, Curzerenone treatment inhibited the tumorigenic activity of cancer cells, and it increased the proportion of CD8 T cells in the xenograft tumor tissues. However, these anti-tumor effects were diminished by the CSNK2B overexpression as well. In conclusion, this research suggests that Curzerenone targets CSNK2B and inactivates the NF-κB signaling to suppress malignancy and immune evasion in cervical cancer.
莪术二酮是传统草药莪术的主要成分，具有潜在的抗癌作用。本研究旨在探讨莪术二酮对宫颈癌细胞的治疗效果及其潜在机制。用莪术二酮处理HeLa和SiHa细胞。100μM莪术二酮处理可抑制细胞的增殖、迁移和侵袭。莪术二酮处理还降低了程序性死亡配体1的细胞表达，这增加了与癌细胞共培养系统中CD8 T细胞的增殖和活性。发现莪术二酮的预测生理靶点酪蛋白激酶2β（CSNK2B）被莪术二酮抑制。进一步过表达CSNK2B可阻断莪术二酮的治疗效果。莪术二酮抑制而CSNK2B触发核因子-κB（NF-κB）途径的激活。CSNK2B的致癌和免疫抑制作用被NF-κB特异性抑制剂阻断。在体内，莪术二酮处理抑制癌细胞的致瘤活性，并增加异种移植肿瘤组织中CD8 T细胞的比例。然而，这些抗肿瘤作用也因CSNK2B的过表达而减弱。总之，本研究表明莪术二酮靶向CSNK2B并使NF-κB信号失活，以抑制宫颈癌的恶性肿瘤和免疫逃逸。
