RESUMEN
BACKGROUND: Recent achievements in cancer therapy are the use of alternating electrical fields at intermediate frequencies (100-300 kHz) and low intensities (1-3 V/cm), which specifically target cell proliferation while affecting different cellular activities depending on the frequency used. METHODS: In this article, we examine the effect of electric fields on spherical suspended cells and propose the combination of Daunorubicin, a chemotherapy agent widely used in the treatment of acute myeloid leukemia, with electric field exposure. U937 cells were subjected to an electric field with a frequency of 200 kHz and an intensity of 0.75 V/cm, or to a combination of Daunorubicin and electric field exposure, resulting in a significant reduction in cell proliferation. Furthermore, the application of an electric field to U937 cells increased Daunorubicin uptake. RESULTS: Apoptosis and DNA damage were induced by the electric field or in conjunction with Daunorubicin. Notably, normal cells exposed to an electric field did not show significant damage, indicating a selective effect on dividing cancer cells (U937). Moreover, the electric field affects the U937 cell line either alone or in combination with Daunorubicin. This effect may be due to increased membrane permeability. CONCLUSIONS: Our findings suggest that the use of electric fields at intermediate frequencies and low intensities, either alone or in combination with Daunorubicin, has potential as a selective anti-cancer therapy for dividing cancer cells, particularly in the treatment of acute myeloid leukemia. Further research is needed to fully understand the underlying mechanisms and to optimize the use of this therapy.
Asunto(s)
Células Sanguíneas , Neoplasias Hematológicas , Humanos , Células U937 , Resultado del Tratamiento , Daunorrubicina/farmacología , Daunorrubicina/uso terapéuticoRESUMEN
Considering the central role of oxidative stress in the onset and progress of Parkinson's diseases (PD), search for compounds with antioxidant properties has attracted a growing body of attention. Here, we compare the neuroprotective effect of bulk and nano forms of the polyphenolic fraction of propolis (PFP) against rotenone-induced cellular and animal models of PD. Mass spectrometric analysis of PFP confirmed the presence of multiple polyphenols including kaempferol, naringenin, coumaric acid, vanillic acid, and ferulic acid. In vitro cellular experiments indicate the improved efficiency of the nano form, compared to the bulk form, of PFP in attenuating rotenone-induced cytotoxicity characterized by a decrease in cell viability, release of lactate dehydrogenase, increased ROS generation, depolarization of the mitochondrial membrane, decreased antioxidant enzyme activity, and apoptosis induction. In vivo experiments revealed that while no significant neuroprotection was observed relating to the bulk form, PFP nanosheets were very effective in protecting animals, as evidenced by the improved behavioral and neurochemical parameters, including decreased lipid peroxidation, increased GSH content, and antioxidant enzyme activity enhancement. We suggest that improved neuroprotective effects of PFP nanosheets may be attributed to their increased water solubility and enrichment with oxygen-containing functional groups (such as OH and COOH), leading to increased antioxidant activity of these compounds.
Asunto(s)
Fármacos Neuroprotectores , Enfermedad de Parkinson , Própolis , Animales , Enfermedad de Parkinson/tratamiento farmacológico , Rotenona/toxicidad , Fármacos Neuroprotectores/farmacología , Própolis/farmacología , Antioxidantes/farmacología , Polifenoles/farmacología , Estrés Oxidativo , Modelos Animales de EnfermedadRESUMEN
Radiation therapy is common in the current procedures of cancer treatment, but in many cases, radiation resistance of cancerous tissue limits efï¬cacy in clinical applications. Therefore, the use of radiosensitizers has been introduced as an effective strategy to increase the efficiency of radiotherapy. Butein (2', 3, 4, 4'-Tetrahydroxychalcone), a polyphenolic compound of flavonoids family, presents anti-cancer properties and inhibits the signaling pathways associated with radiation resistance. Therefore, we hypothesized that butein in combination with radiation may increase radiosensitivity. To evaluate the radiosensitizing effect of butein, we used MKN-45 cell line and performed several assays such as MTT, soft-agar colony formation, apoptosis, cell cycle, and comet assays. Based on obtained results, butein signiï¬cantly enhanced radiosensitivity of MKN-45 cells. Butein treatment abrogated the radiation-induced G2/M cell cycle arrest, increased DNA damage, enhanced apoptosis, and reduced colony-forming ability of irradiated cells. This study on MKN-45 cells demonstrates that combination of butein with radiotherapy increases its radiosensitivity by abrogating the radiation-induced G2/M blockage, impairing DNA repair, and enhancing apoptotic and reproductive cell death. Therefore, we suggest butein as a candidate for combination with radiation therapy to decrease dose of radiation delivered to the patients and its corresponding side effects.