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A novel copper (II) complex activated both extrinsic and intrinsic apoptotic pathways in liver cancerous cells
Author(s) -
Rezaei Azadeh,
Mahmoodi Mehdi,
Mohammadizadeh Fatemeh,
Mohamadi Maryam,
Hajizadeh Mohammad Reza,
Mirzaei Mohammad Reza,
Khanamani Falahatipour Soudeh
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28491
Subject(s) - apoptosis , downregulation and upregulation , microbiology and biotechnology , programmed cell death , chemistry , intrinsic apoptosis , cancer cell , signal transduction , cell , gene , caspase , biology , cancer , biochemistry , genetics
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 50 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.