Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, China.
People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, China.
Sci Rep. 2020 Oct 26;10(1):18235. doi: 10.1038/s41598-020-75173-8.
Pyrazolone complexes have strong anti-tumor and antibacterial properties, but the anti-tumor mechanism of pyrazolone-based copper complexes has not been fully understood. In this study, the possible mechanism and the inhibitory effect of a novel pyrazolone-based derivative compound [Cu(PMPP-SAL)(EtOH)] on human cervical cancer cells (HeLa cells) was investigated. [Cu(PMPP-SAL)(EtOH)] effectively inhibited proliferation of HeLa cells in vitro with an IC value of 2.082 after treatment for 72 h. Cell cycle analysis showed apoptosis was induced by blocking the cell cycle in the S phase. [Cu(PMPP-SAL)(EtOH)] promoted the loss of mitochondrial membrane potential, release of cytochrome c, PARP cleavage, and activation of caspase-3/9 in HeLa cells. Additionally, [Cu(PMPP-SAL)(EtOH)] inhibited the PI3K/AKT pathway and activated the P38/MAPK, and JNK/MAPK pathways. [Cu(PMPP-SAL)(EtOH)] also inhibited the phosphorylation of Iκ-Bα in the NF-κB pathway activated by TNF-α, thus restricting the proliferation of HeLa cells which were activated by TNF-α. In conclusion, [Cu(PMPP-SAL)(EtOH)] inhibited the growth of HeLa cells and induced apoptosis possibly via the caspase-dependent mitochondria-mediated pathway. These results suggest that [Cu(PMPP-SAL)(EtOH)] can be a potential candidate for the treatment of cervical cancer.
吡唑酮类配合物具有很强的抗肿瘤和抗菌性能，但吡唑酮类铜配合物的抗肿瘤机制尚未完全阐明。在这项研究中，研究了一种新型吡唑酮类衍生物化合物[Cu(PMPP-SAL)(EtOH)]对人宫颈癌（HeLa 细胞）可能的作用机制和抑制作用。[Cu(PMPP-SAL)(EtOH)]在体外有效抑制了 HeLa 细胞的增殖，在 72 小时的治疗后 IC 值为 2.082。细胞周期分析表明，通过阻断 S 期细胞周期诱导细胞凋亡。[Cu(PMPP-SAL)(EtOH)]促进了 HeLa 细胞中线粒体膜电位的丧失、细胞色素 c 的释放、PARP 裂解和 caspase-3/9 的激活。此外，[Cu(PMPP-SAL)(EtOH)]抑制了 PI3K/AKT 通路，并激活了 P38/MAPK 和 JNK/MAPK 通路。[Cu(PMPP-SAL)(EtOH)]还抑制了 TNF-α激活的 NF-κB 通路中 Iκ-Bα的磷酸化，从而限制了 TNF-α激活的 HeLa 细胞的增殖。总之，[Cu(PMPP-SAL)(EtOH)]可能通过 caspase 依赖性线粒体介导的途径抑制 HeLa 细胞的生长并诱导细胞凋亡。这些结果表明，[Cu(PMPP-SAL)(EtOH)]可以作为治疗宫颈癌的潜在候选药物。
