Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.819
Filtrar
1.
J Photochem Photobiol B ; 201: 111658, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31710923

RESUMO

The goal of the current experiment is to explore the influence of combined and/or single applications of red and near infrared (NIR) photobiomodulation (PBM) at different wavelengths, energy densities and times on cell viability, population doubling time (PDT), and apoptosis of in vitro cultures of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and h adipose-derived stem cells (hASCs). Both in vitro hBM-MSCs and hASCs were irradiated with 36 protocols using two different laser types (helium­neon [He-Ne] and diodes), four different laser wavelengths (HeNe laser, 630 nm, 810 nm, 630 + 810 nm); three different energy densities (0.6 J/cm2, 1.2 J/cm2, 2.4 J/cm2); and three different PBM times (1, 2, and 3). One-way ANOVA analysis showed that PBM with the 630 nm red laser significantly stimulated cellular viability of both hBM-MSCs and hASCs. The 630 nm red laser significantly decreased PDT of hBM-MSCs. One-way ANOVA demonstrated that the 630 + 810 laser significantly stimulated cellular viability, and significantly decreased PDT and apoptosis of hBM-MSCs and hASCs. Two-way ANOVA analysis showed that PBM with the 630 nm red laser and 630 + 810 nm laser significantly stimulated cellular viability of hASCs compared to the control hASCs, and experimental and control hBM-MSCs. Our study demonstrated that PBM with the combined 630 + 810 nm lasers significantly stimulated cell viability, and significantly decreased PDT and apoptosis of hBM-MSCs and hASCs in vitro. We reported new in vitro evidence where PBM administered at 630 nm (one and two times, 0.6 and 1.2 J/cm2) and 630 + 810 nm (three times, 2.4 J/cm2) significantly increased hASC cell viability compared to its control and the PBM-treated hBM-MSC groups.


Assuntos
Apoptose/efeitos da radiação , Lasers de Gás , Tecido Adiposo/citologia , Células da Medula Óssea/citologia , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Humanos , Terapia com Luz de Baixa Intensidade , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos da radiação , Células-Tronco/citologia , Células-Tronco/metabolismo , Células-Tronco/efeitos da radiação
2.
J Photochem Photobiol B ; 201: 111653, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31710929

RESUMO

Autophagy is an important process for maintaining intracellular homeostasis. Our previous study demonstrated that autophagy was down-regulated in ultraviolet B (UVB)-irradiated keratinocytes. Raffinose is a natural oligosaccharide that serves as a novel activator of autophagy and as a balancing agent to regulate the diversity of environmental stress. However, whether raffinose balances ultraviolet stress through the autophagy activation pathway has yet to be established. In this study, we found that raffinose treatment inhibited the LDH release and trypan blue staining in UVB-challenged human keratinocytes cell line HaCaT but did not affect the cleavage of apoptotic markers Caspase-3 and PARP, as well as translocation into nucleus of other cell death markers Endonuclease G and AIF. Moreover, we confirmed that raffinose treatment enhanced autophagy flux in an MTOR-independent manner in HaCaT cells. Importantly, decrease of LC3-II turnover in UVB-irradiated keratinocytes could be rescued by raffinose treatment, indicating that raffinose treatment increased autophagy in UVB-irradiated HaCaT cells. Furthermore, the effect on cell death by raffinose was inhibited when autophagy was suppressed with either a small interfering RNA targeting ATG5 (siATG5) or autophagic inhibitor wortmannin. In conclusion, we demonstrated that raffinose increases MTOR-independent autophagy and reduces cell death in UVB-irradiated keratinocytes. Our study indicated that the natural agent raffinose presents the potential value in opposing photodamage.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Rafinose/farmacologia , Raios Ultravioleta , Apoptose/efeitos da radiação , Autofagia/efeitos da radiação , Proteína 5 Relacionada à Autofagia/antagonistas & inibidores , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Caspase 3/metabolismo , Linhagem Celular , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo
3.
Anticancer Res ; 39(9): 4805-4810, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519582

RESUMO

BACKGROUND/AIM: Ro 90-7501 has been reported as an inhibitor of the amyloid ß42 fibril assembly that is associated with Alzheimer's disease. The present study aimed to elucidate the radiosensitizing effects of Ro 90-7501 and focused on ATM signaling after irradiation. MATERIALS AND METHODS: Clonogenic survival, apoptosis, and cell-cycle assays as well as western blotting were performed in HeLa cells treated with irradiation and Ro 90-7501. Tumor growth delay assay was also performed using BALB/c-nu mice. RESULTS: The combination of irradiation with Ro 90-7501 showed significant radiosensitizing effects in clonogenic survival and tumor growth delay assays. Ro 90-7501 significantly increased apoptosis and impaired cell cycle after irradiation. Western blotting showed that Ro 90-7501 suppressed the phosphorylation of ATM and its downstream proteins, such as H2AX, Chk1, and Chk2, after irradiation. CONCLUSION: Ro 90-7501 inhibits DNA damage response by inhibiting ATM and has significant radiosensitizing effects on cervical cancer cells.


Assuntos
Aminas/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Benzimidazóis/farmacologia , Radiossensibilizantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Camundongos , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo
4.
Anticancer Res ; 39(9): 5179-5184, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519631

RESUMO

BACKGROUND/AIM: The pesticide dimethoate (O-dimethyl-S- Nmethylcarbamoylmethyl phosphorodithioate) is able to induce severe acute toxicity in living organisms. The aim of this study was to evaluate the effects of ultraviolet radiation, alone or combined with exposure to dimethoate, on the rat skin. MATERIALS AND METHODS: A total of 38 Wistar female rats (Rattus norvegicus albinus), were distributed into four groups: A (n=9) control group, B (n=10) exposed to ultraviolet-B radiation (UV-B), C (n=10) exposed to UV-B followed by application of dimethoate (UV-B+AGRO) and group D (n=9) exposed to dimethoate (AGRO). Histological examination of the tissues, as well as immunohistochemistry for cleaved caspase 3, Ki-67 and COX-2 expression were performed to all groups. RESULTS: Animals submitted to UV-B exhibited hyperkeratosis with moderate cell atypia. Regarding exposure to UV-B+AGRO, the animals presented hyperkeratosis and atrophy, whereas in animals exposed to AGRO, only atrophy was noticed. The immunohistochemical results on skin revealed that UVB, AGRO and UVB+AGRO decreased cleaved caspase 3 and Ki-67 expression when compared to the control group (p<0.05). COX-2 expression decreased to UVB or AGRO groups compared to controls (p<0.05). CONCLUSION: UV-B or AGRO exposure is able to induce histopathological changes and altered expression of cleaved caspase-3 and Ki-67 in rat skin, thus being categorized as a risk condition for skin carcinogenesis.


Assuntos
Dimetoato/farmacologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Raios Ultravioleta , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Feminino , Imuno-Histoquímica , Ratos , Ratos Wistar , Pele/metabolismo
5.
Chem Commun (Camb) ; 55(67): 9971-9974, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31367709

RESUMO

Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses light, oxygen and a photosensitizer to produce localized reactive oxygen species (ROS). Due to the short lifetime of ROS, the location of the photosensitizer in the cell is believed to be the key determinant governing the outcome of PDT. To explore the effect of direct association between a photosensitizer and DNA a well know DNA-binding dye, DAPI, was converted into a photosensitizer. Br-DAPI - unlike native DAPI - upon irradiation produces ROS. We demonstrate that the ROS are only effective in inducing dsDNA breaks when Br-DAPI is bound to DNA. In cancer cells (A549) Br-DAPI causes rapid light dependent cell death. This work supports the design of photosensitizers which bind with high affinity to the DNA of target cells for potentially more effective PDT.


Assuntos
Bromo/química , DNA/química , Indóis/química , Fármacos Fotossensibilizantes/química , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Corantes Fluorescentes/química , Humanos , Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Estudo de Prova de Conceito , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
6.
Life Sci ; 233: 116710, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31369762

RESUMO

AIMS: The naturally occurring compound curcumin has been proposed for a number of pharmacological applications. In spite of the promising chemotherapeutic properties of the molecule, the use of curcumin has been largely limited by its chemical instability in water. In this work, we propose the use of water soluble proteins to overcome this issue in perspective applications to photodynamic therapy of tumors. MATERIALS AND METHODS: Curcumin was bound to bovine serum albumin and its photophysical properties was studied as well as its effect on cell viability after light exposure through MTT assay and confocal imaging. KEY FINDINGS: Bovine serum albumin binds curcumin with moderate affinity and solubilizes the hydrophobic compound preserving its photophysical properties for several hours. Cell viability assays demonstrate that when bound to serum albumin, curcumin is an effective photosensitizer for HeLa cells, with better performance than curcumin alone. Confocal fluorescence imaging reveals that when curcumin is delivered alone, it preferentially associates with mitochondria, whereas curcumin bound to bovine serum albumin is found in additional locations within the cell, a fact that may be related to the higher phototoxicity observed in this case. SIGNIFICANCE: The higher bioavailability of the photosensitizing compound curcumin when bound to serum albumin may be exploited to increase the efficiency of the drug in photodynamic therapy of tumors.


Assuntos
Apoproteínas/metabolismo , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Sistemas de Liberação de Medicamentos , Mioglobina/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Soroalbumina Bovina/metabolismo , Animais , Apoproteínas/química , Apoptose/efeitos da radiação , Bovinos , Sobrevivência Celular , Curcumina/química , Células HeLa , Cavalos , Humanos , Mioglobina/química , Fármacos Fotossensibilizantes/química , Soroalbumina Bovina/química
8.
J Photochem Photobiol B ; 197: 111534, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279897

RESUMO

In the search for developing a biomedicine based nanomaterial for therapeutic applications, here we described a new benign development of Photo-triggered Gold nanodots capped mesoporous silica nanoparticles Au@MSNs loaded with capsaicin (Cap) for photothermal therapy of cancer cells. Electron microscopic techniques (SEM and TEM) studies depict the anisotropic shape of Cap-Au@MSNs with mean size ≈110 nm. The successful amine functionalization and covalent interaction of Au nanodots on the mesoporous silica surface were confirmed from the results of FTIR, XPS and UV-vis spectral analyses, which directly indicates the composition of synthesized mesoporous silica surface. Additionally, Dynamic Light Scattering (DLS) revealed that synthesized cap-AuMSNs were stable with highly negatively charged. Cap-AuMSNs exhibited extraordinary in vitro antitumor activity against the tested twp thyroid cancer cell lines (i.e., FTC-133 and B-CPAP). 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay determined that capsaicin and Cap-AuMSNs conferred strong cytotoxicity against the FTC-133 and B-CPAP cell lines. Further, evaluation of the mechanism showed that anticancer activity was achieved by inducing apoptosis in thyroid cancer cells. In addition, we found that such compounds exhibited promising antimetastatic activity and reduced the invasiveness of cancer cells. Hence, we suggesting that these Cap-Au@MSNs can be used as promising candidates for cancer therapy and deserve further investigation.


Assuntos
Capsaicina/química , Raios Infravermelhos , Nanopartículas/química , Nanoestruturas/química , Dióxido de Silício/química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ouro/química , Humanos , Microscopia Confocal , Fotoquimioterapia , Porosidade , Câncer Papilífero da Tireoide/tratamento farmacológico , Câncer Papilífero da Tireoide/patologia
9.
Cancer Sci ; 110(9): 2834-2845, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31278880

RESUMO

Recurrence and chemoresistance in colorectal cancer remain important issues for patients treated with conventional therapeutics. Metformin and phenformin, previously used in the treatment of diabetes, have been shown to have anticancer effects in various cancers, including breast, lung and prostate cancers. However, their molecular mechanisms are still unclear. In this study, we examined the effects of these drugs in chemoresistant rectal cancer cell lines. We found that SW837 and SW1463 rectal cancer cells were more resistant to ionizing radiation and 5-fluorouracil than HCT116 and LS513 colon cancer cells. In addition, metformin and phenformin increased the sensitivity of these cell lines by inhibiting cell proliferation, suppressing clonogenic ability and increasing apoptotic cell death in rectal cancer cells. Signal transducer and activator of transcription 3 and transforming growth factor-ß/Smad signaling pathways were more activated in rectal cancer cells, and inhibition of signal transducer and activator of transcription 3 expression using an inhibitor or siRNA sensitized rectal cancer cells to chemoresistant by inhibition of the expression of antiapoptotic proteins, such as X-linked inhibitor of apoptosis, survivin and cellular inhibitor of apoptosis protein 1. Moreover, metformin and phenformin inhibited cell migration and invasion by suppression of transforming growth factor ß receptor 2-mediated Snail and Twist expression in rectal cancer cells. Therefore, metformin and phenformin may represent a novel strategy for the treatment of chemoresistant rectal cancer by targeting signal transducer and activator of transcription 3 and transforming growth factor-ß/Smad signaling.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Metformina/farmacologia , Fenformin/farmacologia , Neoplasias Retais/terapia , Transdução de Sinais/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Quimiorradioterapia/métodos , Colo/patologia , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos da radiação , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Masculino , Metformina/uso terapêutico , Camundongos , Camundongos Nus , Recidiva Local de Neoplasia , Fenformin/uso terapêutico , Neoplasias Retais/patologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos da radiação , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Life Sci ; 233: 116685, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31348947

RESUMO

AIMS: The present study aimed to investigate the effects of laser irradiation on the growth factors and cell apoptosis of in vitro cultured infant hemangioma endothelial cells. MAIN METHODS: Endothelial cells of infant hemangioma were cultured in vitro and irradiated using a variable pulse width 1064 nm Nd:YAG laser and intense pulsed light (IPL), the expression of VEGF, VEGFR-2, bFGF and their mRNAs before and after irradiation were measured by ELISA, western blot, RT-PCR and flow cytometry, and changes in the apoptotic rate of endothelial cells in hemangioma were monitored. KEY FINDINGS: The mRNA and protein expressions of VEGF, VEGFR-2, bFGF in hemangioma endothelial cells were inhibited by both Nd:YAG laser and ILP compared to the control cells. The apoptotic rates of hemangioma endothelial cells were also decreased after both laser irradiation treatments in comparison to the blank group. The differences were statistically significant. SIGNIFICANCE: Laser irradiation treats hemangioma not only through a selective photothermal mechanism, but also through cytokine signaling pathways.


Assuntos
Apoptose/efeitos da radiação , Células Endoteliais/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Hemangioma/metabolismo , Hemangioma/patologia , Terapia a Laser/métodos , Proliferação de Células , Citocinas/genética , Citocinas/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Hemangioma/radioterapia , Humanos , Técnicas In Vitro , Lactente , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
11.
Artif Cells Nanomed Biotechnol ; 47(1): 2161-2170, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31159585

RESUMO

Nowadays, there is growing interest regarding the use of metal Nanoshells as targeted agents of Nano-photo thermal cancer therapy. This study was aimed at synthesis the folic acid (FA)-conjugated with silica @gold core-shell nanoparticles (FA-SiO2@AuNPs) for improving the treatment of melanoma cancer cells. The characterization data showed that the FA-SiO2@AuNPs is spherical in shape and its size is ∼73.7 nm. The intracellular uptake of FA-SiO2@AuNPs into melanoma cells (A375) was measured through the inductively coupled plasma, (∼47.7%). The cytotoxicity of nanoparticles was investigated on A375 and HDF (Human dermal fibroblast) cell lines. Cytotoxicity results indicated that there is no significant cytotoxicity in HDF cell lines treated with nanoparticles. MTT and flow cytometry results showed that the viability of A375 cells treated by SiO2@Au and FA-SiO2@AuNPs was decreased significantly to about 31% and 16% respectively. The higher toxicity of cancer cells was obtained for the cells exposed to 808 nm near-infrared (NIR) laser after incubation with FA-SiO2@AuNPs rather than the non-targeted SiO2@AuNPs. Furthermore, about 64% more cell death was observed for A-375 cells using both photothermal therapy and treatment with FA-SiO2@AuNPs compared to photothermal therapy. Additionally, the majority of the cell deaths were related to the apoptosis process, not necrosis. It can be concluded that FA-SiO2@AuNPs was an effective targeting agent for photothermal therapy in the treatment of melanoma.


Assuntos
Ácido Fólico/química , Ouro/química , Ouro/farmacologia , Raios Infravermelhos , Melanoma/patologia , Nanopartículas Metálicas/química , Fototerapia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ácido Fólico/sangue , Humanos , Dióxido de Silício/química
12.
Life Sci ; 232: 116562, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31201845

RESUMO

AIMS: Lung cancer is one of the main causes of cancer-related deaths worldwide and radiotherapy is a major treatment of choice. However, radioresistance is a main reason for radiotherapy failure or tumor relapse. Here, we investigated possible mechanisms associated with cancer cell radioresistance. MATERIALS AND METHODS: We compared two newly derived cell lines, namely A549-IR3 and A549-IR6, which survived repeated (3 or 6 times) 4 Gy exposure of parental A549 lung cancer cell line. DNA repair ability, stemness and senescence were comparatively studied. KEY FINDINGS: A549-IR3 exhibited higher proliferation ability and radioresistance compared to parental and A549-IR6 cells. Enhanced radioresistance was not accompanied by chemoresistance to cisplatin or docetaxel. DNA repair kinetics (γΗ2ΑΧ expression) were similar in all cell lines. A549-IR3 cells exhibited a significant rise in stem cell markers (CD44, CD133, OCT4, SOX2 and NANOG) whereas A549-IR6 displayed an increased senescent population. SIGNIFICANCE: Cancer cells surviving after radiotherapy may follow two different escape pathways: selection for radioresistance resulting in regrowth, and in clinical terms relapse, or above an irradiation threshold, stem-cells die and cancer cells become senescent, leading the tumor to a state of dormancy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Células-Tronco Neoplásicas/efeitos da radiação , Células A549 , Envelhecimento/efeitos da radiação , Apoptose/efeitos da radiação , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Reparo do DNA , Humanos , Neoplasias Pulmonares/metabolismo , Recidiva Local de Neoplasia/genética , Células-Tronco Neoplásicas/metabolismo , Tolerância a Radiação
13.
Int J Mol Sci ; 20(9)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083373

RESUMO

Liquid crystal displays (LCDs) are used as screens in consumer electronics and are indispensable in the modern era of computing. LCDs utilize light-emitting diodes (LEDs) as backlight modules and emit high levels of blue light, which may cause retinal photoreceptor cell damage. However, traditional blue light filters may decrease the luminance of light and reduce visual quality. We adjusted the emitted light spectrum of LED backlight modules in LCDs and reduced the energy emission but maintained the luminance. The 661W photoreceptor cell line was used as the model system. We established a formula of the ocular energy exposure index (OEEI), which could be used as the indicator of LCD energy emission. Cell viability decreased and apoptosis increased significantly after exposure to LCDs with higher emitted energy. Cell damage occurred through the induction of oxidative stress and mitochondrial dysfunction. The molecular mechanisms included activation of the NF-κB pathway and upregulation of the expression of proteins associated with inflammation and apoptosis. The effect was correlated with OEEI intensity. We demonstrated that LCD exposure-induced photoreceptor damage was correlated with LCD energy emission. LCDs with lower energy emission may, therefore, serve as suitable screens to prevent light-induced retinal damage and protect consumers' eye health.


Assuntos
Luz , Cristais Líquidos/química , Células Fotorreceptoras de Vertebrados/patologia , Células Fotorreceptoras de Vertebrados/efeitos da radiação , Animais , Apoptose/efeitos da radiação , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos da radiação , Inflamação/patologia , Camundongos , Mitocôndrias/patologia , Mitocôndrias/efeitos da radiação , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos da radiação , Exposição à Radiação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos da radiação
14.
Life Sci ; 228: 228-241, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31077716

RESUMO

Radio- and chemotherapy are the most common cancer treatment modalities. They cause acute and late side effects on normal tissues, which is a burden for delivery of a high dose of radiation or drugs on tumor cells. In addition, tumor cells achieve adaptive responses to subsequent doses of radiation and chemotherapy, leading to tumor resistance and accelerated repopulation. Resistance to radiotherapy and chemotherapy can occur following adaptive responses, which itself is due to the release of large numbers of inter- and intracellular mediators by immune cells as well as other tumor microenvironment (TME) cells. Melatonin is a potent natural antioxidant and anti-inflammatory agent that protects against toxic side effects of radiation and chemotherapy. Furthermore, in some cancer cells, melatonin aids sensitizing cancer cells to therapy. Apoptosis is one of the main mechanisms of cell death following exposure to radiation and chemotherapy. Evidences have shown a direct relation between apoptosis induction in tumor cells with increased tumor delay regression and survival. Melatonin through modulation of several apoptosis mediators such as mitochondria, Bax, Bcl-2, endogenous ROS, and apoptosis receptors facilitate apoptosis. The current review aims to explain mechanisms of apoptosis induction following exposure to radiation and chemotherapy drugs. We also reviewed the modulatory effect of melatonin on apoptosis signaling pathways.


Assuntos
Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Melatonina/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos da radiação , Humanos , Melatonina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Resultado do Tratamento
15.
Anticancer Res ; 39(5): 2307-2315, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092422

RESUMO

BACKGROUND: Several studies have highlighted hyperthermia's ability to enhance the effectiveness of radiation and chemotherapy in various in vitro and in vivo cancer models. MATERIALS AND METHODS: In vivo murine models of malignant melanoma and colon carcinoma were utilized for demonstrating hyperthermia's therapeutic effectiveness by examining levels of caspase 3, COX-2 and phospho-H2A.X (Ser139) as endpoints of apoptosis, proliferation and DNA damage respectively. RESULTS: Hyperthermia induced in vitro cytotoxicity in malignant melanoma (B16-F10) and colon carcinoma (CT26) cell lines. In addition, it reduced post-in vitro proliferation and suppression of tumor growth by inducing the expression of caspase-3 and phospho-H2A.X (Ser139) while reducing the expression of COX-2 in both murine cancer models. CONCLUSION: Hyperthermia can exert therapeutic effectiveness against melanoma and colon carcinoma by inhibiting a number of critical cellular cascades including apoptosis, proliferation and DNA damage.


Assuntos
Neoplasias do Colo/terapia , Hipertermia Induzida , Melanoma Experimental/terapia , Melanoma/terapia , Animais , Apoptose/efeitos da radiação , Carcinoma/patologia , Carcinoma/terapia , Caspase 3/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias do Colo/patologia , Ciclo-Oxigenase 2/genética , Dano ao DNA/genética , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/genética , Histonas/genética , Humanos , Melanoma/patologia , Melanoma Experimental/genética , Camundongos
16.
Anticancer Res ; 39(5): 2405-2413, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31092433

RESUMO

BACKGROUND/AIM: Plasma medicine is a new field that provides great potential for the treatment of human diseases including cancer in addition to sterilizing the surface of skin and facilitating wound healing. Recently, non-thermal atmospheric plasma (or cold atmospheric plasma, CAP) was introduced, not only for denaturing cells and tissues, but also for operating under the threshold of thermal damage and for chemically inducing a specific response or modification. MATERIALS AND METHODS: Microwave-mediated CAP was used in this study. RESULTS: CAP increased high-mobility group box 1 protein (HMGB1) expression, thereby increasing HMGB-1 secretion. In addition, we observed that the calreticulin (CRT) protein was concentrated at the cellular membrane when plasma was treated, representing immunogenic cell death. CONCLUSION: Overall, plasma treatment induces apoptosis via immunogenic cell death in cancer cells, implying a potential application to human cancer therapy and for the treatment of other human diseases.


Assuntos
Calreticulina/genética , Proteína HMGB1/genética , Neoplasias/terapia , Gases em Plasma/uso terapêutico , Apoptose/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Células HCT116 , Humanos , Fenômenos Imunogenéticos/efeitos da radiação , Micro-Ondas/uso terapêutico , Neoplasias/genética , Neoplasias/patologia
17.
J Photochem Photobiol B ; 195: 39-50, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31075653

RESUMO

Photodynamic therapy (PDT) of cancer uses photosensitizers (PS), a light source and oxygen to generate high levels of reactive oxygen species (ROS), that exert a cytotoxic action on tumor cells. Recently, it has been shown that mixed non-symmetrical diaryl porphyrins, with two different pendants, are more photodynamically active than symmetrical diaryl porphyrins. In the present study, we investigate the in vitro photodynamic effects of four novel non-symmetrical diaryl porphyrins, two of which bear one pentafluoro-phenyl and one bromo-alkyl (apolar) pendant, whereas the two others bear one pentafluoro-phenyl and one cationic pyridine pendant. The four compounds were tested in a small panel of human cancer cell lines, and their photodynamic activities were compared with that of m-THPC (Foscan), currently the most successful PS approved for clinical use in cancer PDT. The results of the cytotoxicity studies indicate that the two molecules bearing the cationic pendant are more potent in vitro than those with the apolar pendant, and that they are as potent as Foscan. To gain further insights into the mechanism of PS-induced phototoxicity, induction of apoptotic, autophagic and necrotic cell death, and generation of reactive oxygen species (ROS) were evaluated in cancer cells following exposure to the PSs and irradiation. The effect of the PSs on the migratory activity of the cells was also assessed. The data obtained from this work support a greater potency of diaryl porphyrins with a positive charge in inducing cell death, as compared to those with the bromo-alkyl pendant; most importantly, some of these novel compounds exhibit features that might make them superior to the clinically approved PS Foscan.


Assuntos
Fármacos Fotossensibilizantes/síntese química , Porfirinas/química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Humanos , Luz , Neoplasias/tratamento farmacológico , Fotodegradação , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
18.
J Med Food ; 22(5): 490-498, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31084541

RESUMO

Although radiation therapy (RT) is a feasible treatment approach for early colorectal cancer, RT is considerably toxic to normal tissues due to the increased reactive oxygen species production, which can induce tissue damage. Ginseng, a natural antioxidant agent, exhibits the protective effects against ionizing radiation (IR)-induced damage in in vitro and in vivo models. The explosive puffing of ginseng has been investigated as a process to improve the efficacy of ginseng due to the resulting physicochemical changes in its functional components. In this study, we provided the evidence for promotion in the beneficial role of puffed ginseng extract (PGE) and associated mechanisms of action, in comparison with white ginseng extract (WGE), against IR-induced colorectal injury, using in vivo study on a mouse model. To study the role of PGE in preventing IR-induced damage, we examined colorectal injury and apoptotic changes in mice exposed to 137Cs at 8 Gy. High-performance liquid chromatography analysis showed that PGE had an increased total ginsenoside concentration with new generation of Rg3, Rg5, and Rk1, compared with the concentrations in WGE. Administering PGE, but not WGE, significantly ameliorated IR-induced colorectal cell death through negative regulation of apoptotic signaling pathways. These antiapoptotic effects of PGE were linked to the capacity to suppress the p53-mediated DNA damage response and NF-κB-mediated apoptotic signaling. Moreover, IR-induced oxidative stress in the colorectal epithelium was markedly reduced by PGE administration. Collectively, this study establishes a mechanism of action by which PGE counteracts IR-induced colorectal injury as a novel radioprotective agent.


Assuntos
Colo/lesões , Ginsenosídeos/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Panax/química , Extratos Vegetais/administração & dosagem , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/efeitos da radiação , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/genética , NF-kappa B/metabolismo , Panax/classificação , Lesões por Radiação/genética , Lesões por Radiação/metabolismo , Radiação Ionizante , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
19.
J Photochem Photobiol B ; 196: 111512, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129505

RESUMO

Cancer is a leading cause of death worldwide, and doxorubicin (DOX) has become one of the most commonly prescribed drugs. Stem cell (SC) therapy is proving to be a promising strategy to alleviate DOX adverse effects on non-cancerous cells. However, the drug also has a toxic action on SCs, reducing the efficiency of cell therapy from a preventive view. The present study shows that the DOX toxicity in mesenchymal SCs (MSCs) can be partially overcome by low-level laser irradiation (LLLI). To achieve this, we applied the low-level red laser (wavelength: 660 nm; output power: 30 mW; laser beam: 0.028 cm2; irradiation: 1.07 mW/cm2; Ga-Al-As Photon Laser III, DMC, São Paulo, Brazil) in rat adipose tissue-derived MSCs before their exposure to different DOX concentrations. Results revealed that the DOX reduced the viability and adenosine triphosphate level of MSCs. These findings were followed by significantly increased apoptosis as well as oxidative stress in the MSCs. Interestingly, LLLI at the dose of 0.2 J alleviated the effects of DOX on cell viability and apoptosis, and inhibited oxidative stress in the MSCs. In summary, this study provides a crucial step toward the future application of LLLI as a protective approach against DOX-induced toxicity in MSCs, particularly cell death. This study also lays the groundwork for further investigation into the role of oxidative stress and inflammation as an instructive milieu for cell protection.


Assuntos
Apoptose/efeitos da radiação , Doxorrubicina/farmacologia , Lasers , Trifosfato de Adenosina/metabolismo , Tecido Adiposo/citologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Citocinas/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Ratos
20.
J Photochem Photobiol B ; 196: 111496, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129507

RESUMO

Surgical resection is one of the most common radical treatments for cancers. However, tumors may be compressed or the local intravascular pressure may be increased during surgical manipulation, causing the shedding and entry of tumor cells into the blood circulation and hence distant recurrence and metastasis of tumors. We have preliminarily established a method of riboflavin photosensitization treatment (RPT) for inactivation of circulating tumor cells. This technology promises to solve the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. In the present study, apoptosis detection and tumorigenicity experiment in immunodeficient mice were conducted to evaluate the effect of RPT for inactivation of circulating tumor cells respectively. Next, functional evaluation was carried out for the immune cells through detecting apoptosis rate and cytokine secretion of lymphocyte. Finally, thromboelastography (TEG) and free hemoglobin were detected to assess peripheral blood coagulation and red blood cell damage. The results showed that RPT (50 µmol/L riboflavin, 10.8 J/cm2 UV) could effectively make tumor cell lose the ability of proliferation in the peripheral blood. In the meantime, the damage caused to peripheral blood coagulation, immune cell function and red blood cells was generally acceptable. The results of the study showed that RPT had huge potential in addressing the problems of shedding and entry of solid tumor cells into blood circulation before surgical manipulation, and almost unavoidable hematogenous dissemination of tumor cells during surgical resection. This therapy is expected to be an auxiliary and supportive method to reduce the risk of hematogenous metastasis and recurrence of cancers, and to increase the surgical success rate of malignant solid tumors.


Assuntos
Células Neoplásicas Circulantes/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Riboflavina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Coagulação Sanguínea/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Células HCT116 , Hemólise/efeitos dos fármacos , Humanos , Luz , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias/tratamento farmacológico , Células Neoplásicas Circulantes/metabolismo , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA