Cytotoxic Effects of Some Flavonoids and Imatinib on the K562 Chronic Myeloid Leukemia Cell Line: Data Analysis Using the Combination Index Method

Background: Flavonoids are natural compounds with antioxidant, anticarcinogenic, and anti-inflammatory effects. Aims: To determine the cytotoxic effects of flavonoids and drug resistance related to P-gp on K562 human chronic myeloid leukemia cells. We also aimed to evaluate the therapeutic potential of imatinib and flavonoid combinations. Study Design: Cell culture study. Methods: In this study, K562 cells were treated with apigenin, luteolin, 5-desmethyl sinensetin and the anticancer drug imatinib mesylate. The effect of flavonoids on K562 cell proliferation was detected using the 3-(4,5-dimethylthiazolyl)2,5­diphenyl­tetrazolium bromide assay. Concentrations of apigenin, luteolin, and 5-desmethyl sinensetin ranging from 25 to 200 µM and of imatinib from 5 to 50 µM administered for 72 h were studied. Apoptosis/necrosis and P-gp activity were measured using flow cytometry. The combined effects of different concentrations of flavonoids with imatinib were evaluated according to combination index values calculated using CompuSyn software. Results: In our study, the IC50 values for apigenin, luteolin, and 5-desmethyl sinensetin were found to be 140 µM, 100 µM, and >200 µM, respectively. Luteolin (100 µM) had the highest cytotoxic activity of these flavonoids. These results were statistically significant (p<0.05). Among the flavonoids studied, the combination of luteolin and imatinib was the most effective and is therefore recommended for its cytotoxic activity in the K562 cell line. After 72 h of incubation at their respective IC50 concentrations, all flavonoids were associated with an apoptosis rate of approximately 50%. P-glycoprotein activity was increased in all groups. Combination treatment may provide better outcomes in terms of cytotoxicity and thus reduce the dosages of imatinib used. Conclusion: The combination of some flavonoids and imatinib mesylate may increase the cytotoxic effect; However, the antagonistic effect should be considered in combined use on k562 cells.

Effects of Luteolin on Liver, Kidney and Brain in Pentylentetrazol-Induced Seizures: Involvement of Metalloproteinases and NOS Activities.

OBJECTIVE: Flavonoids are an important group of recognized antioxidants in plants. Luteolin (LUT) is a natural flavonoid in the plant kingdom. This study was aimed to investigate the effects of the LUT in the liver, kidney and brain of pentylentetrazol (PTZ)-induced seizure and the relationship between nitric oxide synthases (iNOS, eNOS) and matrix metalloproteinases (MMP2, MMP9). MATERIALS AND METHODS: LUT (10 mg/kg) was given intraperitoneally during two weeks prior to seizure induction. A single dose PTZ 80 mg/kg i.p. was administered and seizures were observed and evaluated with regard to latency, frequency and stage for one hour. RESULTS: Seizure frequen cy after PTZ administration was significantly decreased in LUT pretreated rats (p<0.05). An increase of immunhistochemical reactions of iNOS and MMP2, but a decrease of eNOS activity, were observed in rat hippocampus and peripheral tissues during the PTZ induced seizures. LUT pretreatment reversed the iNOS and MMP2 activity to the control levels and significantly increased the eNOS activity (p<0.001). CONCLUSION: LUT seems to have an effective role in reducing the seizure frequency and a protective role on peripheral organ injury in animal models of seizure. The protective effect of LUT in seizures and the seizure induced peripheral tissue damage warrant further investigations.

Cardioactive diterpenes from the roots of Salvia eriophora.

From the roots of Salvia eriophora (Lamiaceae), a new compound, 4,14-dihydroxysaprorthoquinone, was isolated in addition to ten known diterpenoids. The structure of the new compound was established by spectroscopic analysis. The crude extract of the plant and the isolated diterpenoids were tested for their cardiovascular activities using Wistar Albino rats. Activity was demonstrated in the crude extract and in 4,14-dihydroxysaprorthoquinone, aethiopinone, ferruginol, 4,12-dihydroxysapriparaquinone, and 6,7-dehydroroyleanone.