Effects of Menadione, Hydrogen Peroxide, and Quercetin on Apoptosis and Delayed Luminescence of Human Leukemia Jurkat T-Cells

Abstract

Menadione (MD) is an effective cytotoxic drug able to produce intracellularly large amounts of superoxide anion. Quercetin (QC), a widely distributed bioflavonoid, can exert both antioxidant and pro-oxidant effects and is known to specifically inhibit cell proliferation and induce apoptosis in different cancer cell types. We have investigated the relation between delayed luminescence (DL) induced by UV-laser excitation and the effects of MD, hydrogen peroxide, and QC on apoptosis and cell cycle in human leukemia Jurkat T-cells. Treatments with 500 μM H₂O₂ and 250 μM MD for 20 min produced 66.0 ± 4.9 and 46.4 ± 8.6% apoptotic cell fractions, respectively. Long-term (24 h) pre-exposure to 5 μM, but not 0.5 μM QC enhanced apoptosis induced by MD, whereas short-term (1 h) pre-incubation with 10 μM QC offered 50% protection against H₂O₂-induced apoptosis, but potentiated apoptosis induced by MD. Since physiological levels of QC in the blood are normally less than 10 μM, these data can provide relevant information regarding the benefits of flavonoid-combined treatments of leukemia. All the three drugs exerted significant effects on DL. Our data are consistent with (1) the involvement of Complex I of the mitochondrial respiratory chain as an important source of delayed light emission on the 10 μs-10 ms scale, (2) the ability of superoxide anions to quench DL on the 100 μs-10 ms scale, probably via inhibition of reverse electron transfer at the Fe/S centers in Complex I, and (3) the relative insensitivity of DL to intracellular OH• and H₂O₂ levels.

Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthiumL. ethanolic extracts

“…Being an unstable and highly reactive compound, hydrogen peroxide is toxic to cells [28] and known to induce senescence-like growth arrest in human diploid fibroblasts [29]. According to other authors, low concentrations of hydrogen peroxide preferentially induced cell death through apoptosis [30]. …”

Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells

“…M alone has been reported to induce apoptosis [17,18], autophagy in cells with an altered redox state [52], apoptosis and/or necrosis depending on the duration of the treatment [53,54] or autoschizis, when used in combination with vitamin C [55,56]. On the other hand, SO can induce apoptosis or necrosis [30], but it was also found to protect p53-dependent apoptosis [57,58].…”

“…It has shown antiproliferative effects against various kinds of cancer cells, including hepatic [14], oral cavity [15], lung [16], breast [17], bladder [12], leukemia [18] and several glioma cell lines [19][20][21]. However, it has not been considered an efficient therapeutic agent for gliomas due to the systemic toxicity observed at the high concentrations needed for cancer cytotoxicity.…”

Hydrogen peroxide (H2O2) induces leukemic but not normal hematopoietic cell death in a dose-dependent manner

“…The best-explored effect of ROS on cancer cells is its capability to harm or kill them, e.g., by the direct toxicity of H 2 O 2 and nitric oxide [15-17]. Many classes of antineoplastic agents that generates a high level of oxidative stress in biological systems [18], e.g., the synthetic retinoid Fenretinide and diallyl disulfide, promote ROS-dependent cell death in leukemic lineages [19,20].…”