Rezaei Azadeh, Mahmoodi Mehdi, Mohammadizadeh Fatemeh, Mohamadi Maryam, Hajizadeh Mohammad Reza, Mirzaei Mohammad Reza, Khanamani Falahati-Pour Soudeh
Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
J Cell Biochem. 2019 Aug;120(8):12280-12289. doi: 10.1002/jcb.28491. Epub 2019 Feb 21.
Recent advances have put fundamental focus on the application of copper (II) (Cu [II]) complexes as agents for fighting against cancer. To determine whether [Cu(L)(2imi)] complex as a novel Cu complex can induce apoptosis in HepG2 as cancerous cells and L929 as normal cells via extrinsic or intrinsic apoptotic pathways, both cell lines were treated for 24 and 48 hours at IC concentrations of [Cu(L)(2imi)] complex. Then, the expression of some apoptosis-related genes including p53, caspase-8, bcl-2, and bax were assayed by real-time polymerase chain reaction. The [Cu(L)(2imi)] complex seems to inhibit the expression of bcl-2 in complex-treated HepG2 cancerous cells following the 24- and 48-hour treatment. The complex upregulated the p53, bax, and caspase-8 genes, therefore treatment of HepG2 cancerous cells with [Cu(L)(2imi)] complex induces programmed cell death via the upregulation of relative bax/bcl-2 ratio. Finally, this copper complex triggered apoptosis in HepG2 cells via both intrinsic and extrinsic pathway, whereas treatment of normal L929 cells with this complex induce apoptosis only via intrinsic pathway with the upregulation of relative bax/bcl-2 ratio and does not affect the expression level of caspase-8 gene and does not trigger the extrinsic pathway. Finally, these results obtained from present study confirm the role of a novel Cu complex on the induction of apoptosis process in HepG2 and L929 cells by overexpression of bax, inhibition of bcl-2 and increase of the relative bax/bcl-2 ratio. These results support that the [Cu(L)(2imi)] complex is able to induce apoptosis in cancerous cells, therefore, it has a potential for development as a novel anticancer drug.
最近的进展使人们将基本重点放在了铜（II）（Cu [II]）配合物作为抗癌剂的应用上。为了确定新型铜配合物[Cu(L)(2imi)]是否能通过外源性或内源性凋亡途径诱导肝癌细胞HepG2和正常细胞L929凋亡，两种细胞系均在[Cu(L)(2imi)]配合物的半数抑制浓度（IC）下处理24小时和48小时。然后，通过实时聚合酶链反应检测一些凋亡相关基因的表达，包括p53、半胱天冬酶-8、bcl-2和bax。在处理24小时和48小时后，[Cu(L)(2imi)]配合物似乎抑制了经其处理的HepG2癌细胞中bcl-2的表达。该配合物上调了p53、bax和半胱天冬酶-8基因，因此用[Cu(L)(2imi)]配合物处理HepG2癌细胞可通过上调相对bax/bcl-2比值诱导程序性细胞死亡。最后，这种铜配合物通过内源性和外源性途径触发HepG2细胞凋亡，而用该配合物处理正常L929细胞仅通过内源性途径诱导凋亡，伴随着相对bax/bcl-2比值的上调，且不影响半胱天冬酶-8基因的表达水平，也不触发外源性途径。最后，本研究获得的这些结果证实了一种新型铜配合物通过过表达bax、抑制bcl-2和增加相对bax/bcl-2比值在诱导HepG2和L929细胞凋亡过程中的作用。这些结果支持[Cu(L)(2imi)]配合物能够诱导癌细胞凋亡，因此，它有作为一种新型抗癌药物开发的潜力。
