Apoptotic effect of novel pyrazolone-based derivative [Cu(PMPP-SAL)(EtOH)] on HeLa cells and its mechanism

Abstract

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 IC50 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.

Cu(ii) complexes with a salicylaldehyde derivative and α-diimines as co-ligands: synthesis, characterization, biological activity. Experimental and theoretical approach

“…The observed proapoptotic activities of our newly synthesized Cu( ii ) complexes in cervical adenocarcinoma HeLa cells are in line with the reported abilities of different Cu( ii ) complexes to induce apoptotic cell death in various types of cancer cell lines. 76,77,79–82 Diverse Cu( ii ) complexes which contain 2,2′-bipyridine or 1,10-phenanthroline as a ligand have been shown to trigger apoptosis in HeLa cells as well. 77,79,81,82 Considering the fact that both the tested Cu( ii ) complexes demonstrated similar proapoptotic activity (similar percentage of dead HeLa cells, as measured by cell cycle analysis in cell samples treated with 2IC 50 concentrations), the Cu( ii ) complex 2 which contains 1,10-phenanthroline as a ligand was more active in triggering apoptosis when compared with the Cu( ii ) complex 1 which contains 2,2′-bipyridine as a ligand because complex 2 was used at remarkably lower concentrations.…”

Sanghuangporus sanghuangextract inhibits the proliferation and invasion of lung cancer cellsin vitroandin vivo

“…The imbalance between cell proliferation and the cell death signals is the main characteristic of cancer. Therefore, inhibiting cell growth and inducing apoptosis may be the main strategy for cancer therapy [ 19 ]. This study found that SAE could remarkably inhibit the proliferation and DNA synthesis rate of A549 and H1650 cells in a dose and time-dependent manner.…”

The Effect of Recombinant Fusion Peptide Capsular Biosynthesizing Enzymes A, C Streptococcus agalactiae and Anti-Cancer Peptide against Cell Line Hela by Real-time RT- PCR and Flow cytometry

“…In the present study, the caspase-3 apoptotic mRNA expression elevated and the expression of Bax and Bcl-2 apoptotic mRNAs decreased. After the treatment of HeLa cells with the recombinant fusion peptide, their morphology changed and HeLa cancer cells shifted from an epithelial form, which indicated apoptosis and the effect of the recombinant fusion peptide on cancer cells [30][31].…”