Cytotoxic and Genotoxic Effects of the Quercetin/Lanthanum Complex on Human Cervical Carcinoma Cells In Vitro

Abstract

Quercetin is the main fl avonoid in diet with a potential in the treatment of cancer, cardiovascular, and neurodegenerative diseases. Due to its specifi c planar chemical structure, quercetin readily forms chelates with metal ions. Complexes of bioactive compounds and metal ions such as lanthanum often show strong cytotoxic and antitumour properties. The aim of this study was to compare the genotoxic effects of the quercetin/lanthanum complex on human cervical carcinoma cells with compare it to the effects of free ligands, quercetin, and lanthanum alone. The quercetin/lanthanum complex showed considerable cytotoxicity in the concentration range of (100 to 1000) mmol mL -1 and exposure time of three hours. The complex also induced a dose-dependent pro-oxidative effects and the formation of single-strand and double-strand DNA breaks. Although we obtained promising results on the cell level, future experiments should answer whether the quercetin/lanthanum complex is cancer-specific and stable enough in physiological conditions to make a potential new antitumour drug. Arh Hig Rada Toksikol 2011;62:221-227 Evidence abounds about antitumour activity of small-molecule compounds, including metal complexes with fl avonoids, which directly interact with DNA (1). Recently, much attention has also been paid to how cancer cell growth and apoptosis are affected by rare earth metals and compounds such as lanthanum and cerium salts (2, 3). KEY WORDS: chelates, DNA damage, fl avonoid/metal complexes, oxidative damage Durgo K et al. QUERCETIN/LANTHANUM COMPLEX EFFECTS ON HUMAN CERVICAL CARCINOMA CELLSLanthanum salts can arrest the cell cycle in the G1/S phase in leukemic cell lines (2) and inhibit telomerase activity in the lymphoblastoid tumour cell line (3). Both induce apoptotic events. Contrary to this effect observed in tumour cells, no effect could be determined in normal bone marrow haematopoietic cells (2). Lanthanum complexed with bioactive compounds from plants has shown even stronger cytotoxic effect than when administered alone (4), suggesting that electron transfer and oxidative stress are responsible for the cytotoxic effect. Kostova et al. (5) found that lanthanum complexes with biscoumarins caused apoptotic cell death of several leukaemia and lymphoma cell lines, causing DNA fragmentation and morphological changes. The authors believe that this cytotoxic effect depends on the metal-ligand structure. Wang et al. (1) analysed a lanthanum-naringenin Schiff-base complex and found that the ligands were coordinated to the lanthanum ion through deprotonated hydroxyl groups. This complex bound directly to calf-thymus DNA, probably through intercalation, while the same concentrations caused a strong cytotoxic effect on human leukaemia and lung adenocarcinoma cells. Intercalation is the main cytotoxic mechanism of numerous antitumour agents such as cisplatin, but their use is limited by drug resistance. Determination and synthesis of new agents

Flavonoid–Metal Ion Complexes: A Novel Class of Therapeutic Agents

“…However, the exact mechanism for such activity is yet to be fully elucidated. Quercetin–metal ion complexes, especially, have been reported to exhibit anticancer activities similar to the parent flavonoid . Whether the complex also acts on identical cellular targets as quercetin remains to be explored.…”

“…The anticancer potency of the flavonoid–metal ion complexes in many cases has been found to be greater than the parent flavonoids. Several reports have highlighted the effectiveness of the flavonoid–metal ion complexes against human cervical carcinoma cells, gastric cancer cells, human hepatocellular liver carcinoma cells, leukemia cells, human colon adenocarcinoma cells, human hepatoma cells, and osteoblast cancer cells …”

Role of Aryl Hydrocarbon-Ligands in the Regulation of Autoimmunity

“…ROS production by quercetin was found to kill some cancer cells, and quercetin complexes with bioactive compounds and metal ions such as lanthanum was reported to have powerful cytotoxic and antitumor properties at a concentration in the range of 100-1000 mM and the exposure time of tumor cells was around 3 hours. A quercetin/lanthanum complex was found to have a genotoxic effect on human cervical carcinoma cells due to ROS production [76].…”

Metal based drugs and chelating agents as therapeutic agents and their antimicrobial activity

“…Following metal atoms: Cu(II), Ni(II), Fe(II), Zn(II), Co(II), Cd(II), Pt(II), Mo(II), Pd(II), Mn(II), Hg(II), Lu(III), La(III), Gd(III), Al(III), Fe(III), Eu(III) and VO(IV) majorly form complex with flavonoids. [65][66][67][68][69][70][71][72][73][74][75]…”