The Mechanism for Anticancer and Apoptosis‐Inducing Properties of Cu(II) Complex with Quercetin and 1,10‐Phenanthroline

Abstract

This article covers the anticancer activities and mechanisms of action of Cu(II) complexes of flavonoid‐derived quercetin and 1,10‐phenanthroline ligands. The antiproliferative activity of the complex and its ligands was evaluated by MTT, ATP, and SRB viability assays in human lung cancer cells (A549, H1299). Findings for apoptosis were determined by fluorescent staining, flow cytometry analysis, and the M30 antigen method. In addition, the mechanism of action of the complex was investigated by Annexin V staining, caspase 3/7 activity, ROS formation, and cell cycle analysis. The involvement of caspases, thus, apoptosis was confirmed by rescuing cell death by using a pan‐caspase inhibitor (Z‐VAD‐FMK). Again, increased ROS levels in the cell showed that death may occur by apoptosis. For this reason, the accuracy of ROS‐induced apoptosis in cells has been proven as a result of the application of N‐acetylcysteine (NAC), which is a ROS inhibitor. The efficacy of the complex was compared with Cisplatin and ligands. The results showed that the Cu(II) flavonoid complex is cytotoxic on lung cancer cells and may have the potential to act as an effective metal‐based anticancer drug with a lower IC50 over Cisplatin.

Soloxolone methyl induces apoptosis and oxidative/ER stress in breast cancer cells and target cancer stem cell population

“…The tagged cells were laser exposed after being pumped under pressure via a capillary tube known as a “flow cell”. The instrument and kit compatible with Muse TM Cell Analyzer (Millipore, Germany) were utilized ( Done et al, 2022 ).…”

Investigation of novel Mn(ii) fenamato complexes with neocuproine and their effects on endometrial cell lines

“…Recent studies indicate that certain NSAIDs, such as naproxen or ibuprofen, can inhibit caspases and the apoptotic pathway, 38 metal complexes with 1,10phenanthroline based ligands are known to induce apoptosis in various cancer cell lines. 39,40 Results of the caspase assay (Table 2) indicate different effects of 1 and 2 on the studied cell lines at 10 mM dosage. The activity of executive caspases 3 and 7 was significantly enhanced in 12Z endometriotic cells treated with 2, with almost a two-fold increase compared to the hTERT HME1 cell line, while both complexes induced only a slight increase in caspase activity in the SK-UT-1 cell line (Fig.…”

Copper(II) Complexes with 1-(Isoquinolin-3-yl)heteroalkyl-2-ones: Synthesis, Structure and Evaluation of Anticancer, Antimicrobial and Antioxidant Potential

“…For example, the antiproliferative effect of copper(II) complexes results from the inhibition of the activities of enzymes, which play a pivotal role in cancer therapy, e.g., protein disulfide isomerase (PDI) [ 20 ], topoisomerases I and II [ 21 , 22 , 23 ], telomerase [ 24 ] or proteasome [ 25 , 26 , 27 ], as well as DNA intercalation [ 28 , 29 , 30 ] and DNA degradation [ 31 , 32 ]. Moreover, the antitumor activity of copper compounds may also be the consequence of their ability to induce apoptosis [ 33 , 34 ] and non-apoptotic cell death—paraptosis [ 25 , 35 ]—reactive oxygen species (ROS) formation that triggers tumor cell death [ 36 , 37 ], and antiangiogenic properties [ 38 ]. In turn, the copper(II) complex with disulfiram , a drug used in humans to treat alcoholism with great potential for the treatment of human cancers [ 39 ], was found to be capable of reversing the drug resistance of doxorubicin (ADM)-resistant acute leukemia cell lines by the induction of apoptosis [ 40 ].…”