Treatment of cervical cancer by electrochemotherapy with bleomycin, cisplatin, and calcium: an in vitro experimental study.

Low-dose chemotherapy in advanced stages of cancer does not give a positive response in treatment. The use of high-dose antineoplastic drugs creates significant side effects. The limiting situation in treatment creates a need for new generation drugs with less side effects and new treatment methods that will enable low-dose drug use. Electroporation (EP), a phenomenon, is a technique in which the membrane permeability is increased by the establishment of hydrophilic pores in the cell membrane with short and high-voltage electrical pulses. In the present investigation study, we aimed to inspect the effects of EP plus bleomycin, cisplatin, and calcium administration (CaEP) on cell viability, apoptotic activity, gene expression p53, Bax/Bcl-2 rate mitochondrial membrane potential (ΔΨm), and cell cycle in HeLa cervical cancer cell line. The permeabilization of the membrane was evaluated in flow cytometry with the PI method, and cell viability was measured in an ELISA reader with the WST-8 method. For bleomycin and cisplatin doses applied to HeLa cells, the concentration values (IC50) that inhibited 50% of the cells were found to be 214.11 ± 4.7 µM and 35.16 ± 3.3 µM, respectively. The IC50 values of the groups administered together with EP were calculated as 0.44 ± 0.3 µM for bleomycin and 20.55 ± 4.3 µM for cisplatin. There was no change in cell viability in calcium alone application, but a statistically notable reduction in cell vitality was observed in CaEP application. An increase in ΔΨm was found in bleomycin and CaEP exposure with EP. It was determined that EP exposure caused G0/G1 arrest in the cell cycle at all electric field intensities. It was determined that EP application in HeLa cells increased bleomycin cytotoxicity 487 times and cisplatin cytotoxicity 1.71 times, and CaEP could be an alternative treatment method.

Tea extracts protect normal lymphocytes but not leukemia cells from UV radiation-induced ROS production: An EPR spin trap study.

PURPOSE: An ex vivo method for detection of free radicals and their neutralization by aqueous tea in human normal lymphocytes and MEC-1 leukemia cells under ultraviolet (UV) irradiation was investigated. MATERIALS AND METHODS: This method is based on the electron paramagnetic resonance (EPR) spectroscopy spin-trapping technique. 5-tert-butoxycarbonyl 5-methyl-1-pyrroline N-oxide (BMPO) was used as the spin trap. Normal human lymphocytes and leukemia cells were exposed to UVB radiation (290-315 nm) at 47.7 and 159 mJ/cm(2) and to UVA radiation (315-400 nm) at 53.7 J/cm(2). RESULTS: No significant radical production at 47.7 mJ/cm(2) UVB dose in both cell lines was observed. In normal cells, free radical production was observed at 159 mJ/cm(2) UVB and 53.7 J/cm(2) UVA doses. However, both UV sources did not significantly produce free radicals in leukemia cells. A radical scavenging property of tea extracts (black, green, sage, rosehip) was observed in normal lymphocytes after both UVB and UVA exposure. In leukemia cells, the intensities of EPR signals produced in BMPO with tea extracts were found to be increased substantially after UVA exposure. CONCLUSION: These results showed that UV radiation induced free radical formation in normal human lymphocytes and indicated that tea extracts may be useful as photoprotective agents for them. On the other hand, tea extracts facilitated free radical production in leukemia cells.

Mutagenic and morphologic impacts of 1.8GHz radiofrequency radiation on human peripheral blood lymphocytes (hPBLs) and possible protective role of pre-treatment with Ginkgo biloba (EGb 761).

The mutagenic and morphologic effects of 1.8GHz Global System for Mobile Communications (GSM) modulated RF (radiofrequency) radiation alone and in combination with Ginkgo biloba (EGb 761) pre-treatment in human peripheral blood lymphocytes (hPBLs) were investigated in this study using Sister Chromatid Exchange (SCE) and electron microscopy. Cell viability was assessed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction assay. The lymphocyte cultures were exposed to GSM modulated RF radiation at 1.8GHz for 6, 8, 24 and 48h with and without EGb 761. We observed morphological changes in pulse-modulated RF radiated lymphocytes. Longer exposure periods led to destruction of organelle and nucleus structures. Chromatin change and the loss of mitochondrial crista occurred in cells exposed to RF for 8h and 24h and were more pronounced in cells exposed for 48h. Cytoplasmic lysis and destruction of membrane integrity of cells and nuclei were also seen in 48h RF exposed cells. There was a significant increase (p<0.05) in SCE frequency in RF exposed lymphocytes compared to sham controls. EGb 761 pre-treatment significantly decreased SCE from RF radiation. RF radiation also inhibited cell viability in a time dependent manner. The inhibitory effects of RF radiation on the growth of lymphoctes were marked in longer exposure periods. EGb 761 pre-treatment significantly increased cell viability in RF+EGb 761 treated groups at 8 and 24h when compared to RF exposed groups alone. The results of our study showed that RF radiation affects cell morphology, increases SCE and inhibits cell proliferation. However, EGb 761 has a protective role against RF induced mutagenity. We concluded that RF radiation induces chromosomal damage in hPBLs but this damage may be reduced by EGb 761 pre-treatment.