1,720,972 research outputs found
The neuroleptic drug Fluphenazine induces a significant UVA-mediated cytotoxic effect on three human cancer cell lines through apoptosis
No full textThe cytotoxic activity of fluphenazine (FPZ) in combination with UVA light was evaluated on three human tumor cell lines, HeLa, MSTO-211H and A431. The photobiological effect was determined following irradiation treatment in the presence of/or after the removal of incubated FPZ. Under both conditions, FPZ proved to be very effective in killing tumor cells, with GI50 values in the micromolar range. However, when FPZ was present during irradiation, the photocytotoxicity was at least two times higher than that after its removal suggesting the contribution of the drug both outside and inside the cells. The uptake of FPZ was very fast and, after only 15 minutes of incubation, the compound was accumulated inside lysosomes, as evidenced through fluorescence microscopy. FPZ distribution covered also the nucleus and the cytoplasm without significant plasma membrane association. After irradiation, the membrane of lysosomes in which FPZ was accumulated lost its integrity suggesting that the released lysosomal enzymes played an important role in cell death, and mitochondria were damaged as well, following apoptosis. Indeed, cytofluorimetric studies demonstrated that apoptosis was the main mechanism of cell death. Finally, an extremely high production of ROS was found, indicating a significant photodynamic mechanism involved in the photocytotoxic effect of FPZ. Taken together, our data show that FPZ following UVA irradiation behaves as an effective photoantiproliferative compound inducing apoptosis on various human tumor cells
PBL (Psoralens + Blue light): how blue light activates furocoumarin derivatives triggering tumor cell apoptosis
No full textBACKGROUND. Furocoumarins are natural and synthetic compounds with high chemotherapeutic potency under UVA irradiation. To improve their activity and avoid severe side effects likely mainly related to the formation of interstrand crosslinks (XLs) with DNA pyrimidine bases, a variety of derivatives, hopefully monofunctionals, have been synthesized. Although angelicins, due to their angular geometry, do not generally form XLs, some of them, i.e. (TMA), can crosslink folded DNA upon UVA. The UVA photobiological effects of furocoumarins are mainly related to their capacity to photoreact with DNA. Furthermore, furocoumarins produce ROS that impair cellular functions through lipid peroxidation, oxidation of guanine and strand breaks in nucleic acids, oxidation of proteins and inactivation of enzymes.
To photoactivate 8- MOP and 4,6,4'-trimetylangelicin (TMA) towards human prostate (DU145 PCa) and bladder (T24) cancer cell lines, a new approach based on less toxic and more penetrating visible radiation (BL, 420 nm) is presented.
RESULTS. TMA and 8-MOP show high antiproliferative activity towards cancer cells, through induction of apoptosis. Besides ROS generation (less efficient under BL than UVA), the proapoptotic effect seems related to the activation of p38 and inhibition of p44/42 phosphorylation. Interestingly, the decrease of β nuclear-catenin is coupled with dropping of CD44-positive cells. The strong photocytotoxicity of TMA and 8-MOP can be related to the kind and number of DNA lesions. Under BL, no mutagenic crosslinks, no photocleavage nor photooxidative lesions are detected on isolated DNA by TMA treatment, but only MAs form. However, formation of XLs still remains for 8-MOP under BL but in a lower amount than UVA.
CONCLUSIONS. Overall, our results indicate that 8-MOP, and particularly TMA, can be efficiently activated by BL and may be considered good compounds for targeted phototherapy of prostate and bladder cancers and possibly for other solid tumors
PBL (PSORALENS + BLUE LIGHT): BLUE LIGHT ACTIVATES 8-MOP AND TMA TRIGGERING PROSTATE (DU145) AND VESICAL (T24) TUMOR CELL APOPTOSIS AND DEATH
No full textBACKGROUND. Psoralens and angelicins (furocoumarins) are natural and synthetic compounds with high antiproliferative potency under UVA irradiation mainly used for the treatment of skin diseases (PUVA therapy) or immunological disorders in extracorporeal photopheresis (ECP). To improve their activity against psoriasis or vitiligo and avoid severe side effects mainly related to the formation of interstrand crosslinks (XLs) with DNA pyrimidine bases, a variety of derivatives, hopefully monofunctional, have been synthesized. Although angelicins, due to their angular geometry, do not generally form XLs, some of them, i.e. (TMA), can crosslink folded DNA upon UVA. Furthermore, furocoumarins produce ROS that impair cellular functions through lipid peroxidation, oxidation of guanine and strand breaks in nucleic acids, oxidation of proteins and inactivation of enzymes.
To photoactivate 8- MOP and 4,6,4'-trimetylangelicin (TMA) towards human prostate (DU145 PCa) and bladder (T24) cancer cell lines, a new approach based on less toxic and more penetrating visible radiation (BL, 420 nm) is proposed.
RESULTS. TMA and 8-MOP showed high antiproliferative activity towards both cancer cell lines, through induction of apoptosis. Besides ROS generation (less efficient under BL than UVA), the proapoptotic effect seemed related to the activation of p38 and inhibition of p44/42 phosphorylation. Moreover, no phosphorylation of the histone H2AX, nuclear β -catenin and GSK3β occurred. Moreover, Cyclin D1, c-Myc and CD44v6 expression were reduced through inhibition of the Wnt pathway. Overall, DU145 cells appeared more sensitive to PBL than T24, showing a specificity of the test compounds towards different tumor cell lines. The strong photocytotoxicity of TMA and 8-MOP can be related to the kind and number of DNA lesions. Under BL, no mutagenic crosslinks, no photocleavage nor photooxidative lesions were detected on isolated DNA by TMA phototreatment, but only MAs can form. However, generation of XLs still remained for 8-MOP under BL but in a lower amount than under UVA.
CONCLUSIONS. Overall, our results indicate that 8-MOP, and particularly TMA, can be efficiently activated by BL and may be considered good candidates for targeted PBL of prostate and bladder cancers and possibly for other solid tumors
Mesenchymal Stem Cell Membrane-Coated TPCS2a-Loaded Nanoparticles for Breast Cancer Photodynamic Therapy
Full text linkDespite substantial improvements in breast cancer (BC) treatment there is still an urgent need to find alternative treatment options to improve the outcomes for patients with advanced-stage disease. Photodynamic therapy (PDT) is gaining a lot of attention as a BC therapeutic option because of its selectivity and low off-target effects. However, the hydrophobicity of photosensitizers (PSs) impairs their solubility and limits the circulation in the bloodstream, thus representing a major challenge. The use of polymeric nanoparticles (NPs) to encapsulate the PS may represent a valuable strategy to overcome these issues. Herein, we developed a novel biomimetic PDT nanoplatform (NPs) based on a polymeric core of poly(lactic-co-glycolic)acid (PLGA) loaded with the PS meso-tetraphenylchlorin disulfonate (TPCS2a). TPCS2a@NPs of 98.89 ± 18.56 nm with an encapsulation efficiency percentage (EE%) of 81.9 ± 7.92% were obtained and coated with mesenchymal stem cells-derived plasma membranes (mMSCs) (mMSC-TPCS2a@NPs, size of 139.31 ± 12.94 nm). The mMSC coating armed NPs with biomimetic features to impart long circulation times and tumor-homing capabilities. In vitro, biomimetic mMSC-TPCS2a@NPs showed a decrease in macrophage uptake of 54% to 70%, depending on the conditions applied, as compared to uncoated TPCS2a@NPs. Both NP formulations efficiently accumulated in MCF7 and MDA-MB-231 BC cells, while the uptake was significantly lower in normal breast epithelial MCF10A cells with respect to tumor cells. Moreover, encapsulation of TPCS2a in mMSC-TPCS2a@NPs effectively prevents its aggregation, ensuring efficient singlet oxygen (1O2) production after red light irradiation, which resulted in a considerable in vitro anticancer effect in both BC cell monolayers (IC50 < 0.15 μM) and three-dimensional spheroids
A Study on Photostability of Ethyl Glucuronide in Hair Irradiated under Artificial Sunlight
No full textDrugs incorporated into hair are exposed to the environment, and cosmetic and chemical treatments, with possible decreases in their content. Knowledge concerning the effect of sunlight on drug content in hair can be helpful to forensic toxicologists, in particular, when investigating drug concentrations above or below pre-determined cut-offs. Twenty-eight authentic positive hair samples were selected which had previously tested positive for ethyl glucuronide (EtG). Washed hair were divided into two identical tufts, with the former exposed at 13,219 J/cm2 (300-800 nm spectrum of irradiance) for 48 h in a solar simulator, and the latter kept in the dark. Hair samples were extracted and analyzed by ultra performance liquid chromatography-tandem mass spectrometry. The percentage of photodegradation was calculated for EtG. In parallel, photodegradation processes of standard molecule dissolved in aqueous and organic solutions were studied. In 28 hair samples, positive for the targeted analyte, exposure to artificial sunlight induced an appreciable increase in EtG concentrations. The concentration range in the non-irradiated hair samples was 6.0-772.0 pg/mg, and 64.3% of samples exhibited an increase in post-irradiation samples, ranging from 7% to 255%. In seven cases, a decrease was observed ranging from -5.0% to -36.0%. Thus, either a decrease or an increase of EtG may be observed post-irradiation, depending on hair color and/or hair thickness. Because the denaturation status of hair fibers and the thickness of hair before irradiation could play a role, a scanning electron microscope study should be envisaged
Correction to: Analysis of Radiation Toxicity in Mammalian Cells Stably Transduced with Mitochondrial Stat3
No full textCorrection to Int. J. Mol. Sci. 2023, 24(9), 823
4,6,4′-trimethylangelicin photoactivated by blue light might represent an interesting option for photochemotherapy of non-invasive bladder carcinoma: An in vitro study on T24 cells
Full text linkPhotodynamic therapy (PDT) is frequently used to treat non-muscle invasive bladder cancer due its low toxicity and high selectivity. Since recurrence often occurs, alternative approaches and/or designs of combined therapies to improve PDT effectiveness are needed. This work aimed to evaluate the cytotoxicity of 4,6,4′-trimethylangelicin (TMA) photoactivated by blue light (BL) on human bladder cancer T24 cells and investigate the mechanisms underlying its biological effects. TMA/BL exerted antiproliferative activity through the induction of apoptosis without genotoxicity, as demonstrated by the expression levels of phospho-H2AX, an indicator of DNA double-stranded breaks. It also modulated the Wnt canonical signal pathway by increasing the phospho-β-catenin and decreasing the nuclear levels of β-catenin. The inhibition of this pathway was due to the modulation of the GSK3β phosphorylation state (Tyr 216) that induces a proteasomal degradation of β- catenin. Indeed, a partial recovery of nuclear β-catenin expression and reduction of its phosphorylated form after treatment with LiCl were detected. As demonstrated by RT-PCR and cytofluorimetric analysis, TMA/BL also decreased the expression of CD44v6, a marker of cancer stem cells. Taken together, our data suggest that TMA photoactivated by BL may represent an interesting option for the photochemotherapy of noninvasive bladder carcinomas, since this treatment is able to inhibit key pathways for tumour growth and progression in the absence of genotoxic effects
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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