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1.
In Vivo ; 35(5): 2599-2608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410947

RESUMO

BACKGROUND/AIM: Asian Traditional medicines are renowned for their antitumor properties and are efficacious in the clinical treatment of various cancer types. ERM210 is a Korean traditional medicine comprising nine types of medicinal plants. In the present study, we examined the pro-apoptotic effect and molecular mechanisms of the effects of ERM210 on HepG2 liver cancer cells. MATERIALS AND METHODS: The cytotoxicity of ERM210 on HepG2 cells was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound-healing assays, and apoptosis and signaling pathways by fluorescence microscopy flow cytometry and western blotting. RESULTS: ERM210 significantly impaired HepG2 cell viability and enhanced mitochondria-dependent cellular apoptosis in a time- and dose-dependent manner by up-regulating the expression of caspases 3, 7 and 9, and of BCL2 apoptosis regulator (BCL2)-associated X, apoptosis regulator (BAX) proteins, whilst down-regulating that of BCL2 protein. Furthermore, ERM210 treatment increased accumulation of cellular and mitochondrial reactive oxygen species (ROS) and significantly inhibited cell migration. Additionally, all these phenomena were reversed by treating with the ROS scavenger N-acetylcysteine. The analysis of signaling proteins revealed that ERM210 significantly up-regulated the phosphorylation of ROS-dependent mitogen-activated protein kinases (p38, extracellular-regulated kinase, and c-Jun N-terminal kinase in HepG2 liver cancer cells. CONCLUSION: ERM210 exerts anticancer effects in HepG2 liver cancer cells by up-regulating ROS/mitochondria-dependent apoptosis signaling, providing new insight into the possibility of employing this traditional medicine for the clinical treatment of liver cancer.


Assuntos
Apoptose , Neoplasias Hepáticas , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
Aging (Albany NY) ; 13(10): 13926-13940, 2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030134

RESUMO

Peroxiredoxin II (Prx II) is involved in proliferation, differentiation, and aging in various cell types. However, Prx II-mediated stem cell regulation is poorly understood. Here, dermal mesenchymal stem cells (DMSCs), cell-growth factor-rich conditioned medium from DMSCs (DMSC-CM), and DMSC-derived exosomes (DMSC-Exos) were used to explore the regulatory role of Prx II in DMSC wound healing. Following treatment, wound healing was significantly decelerated in Prx II-/- DMSCs than in Prx II+/+ DMSCs. In vitro stimulation with 10 µM H2O2 significantly increased apoptosis in Prx II-/- DMSCs compared with Prx II+/+ DMSCs. The mRNA expression levels of EGF, b-FGF, PDGF-B, and VEGF did not significantly differ between Prx II-/- and Prx II+/+ DMSCs. Fibroblasts proliferated comparably when treated with Prx II+/+ DMSC-CM or Prx II-/- DMSC-CM. Wound healing was significantly higher in the Prx II-/- DMSC-Exos-treated group than in the Prx II+/+ DMSCs-Exos-treated group. Moreover, microRNA (miR)-21-5p expression levels were lower and miR-221 levels were higher in Prx II-/- DMSCs than in Prx II+/+ DMSCs. Therefore, our results indicate that Prx II accelerated wound healing by protecting DMSCs from reactive oxygen species-induced apoptosis; however, Prx II did not regulate cell/growth factor secretion. Prx II potentially regulates exosome functions via miR-21-5p and miR-221.


Assuntos
Derme/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Peroxirredoxinas/metabolismo , Cicatrização , Animais , Apoptose , Meios de Cultivo Condicionados/farmacologia , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Exossomos/ultraestrutura , Deleção de Genes , Peróxido de Hidrogênio/toxicidade , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos Knockout , MicroRNAs/genética , MicroRNAs/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Cicatrização/genética
3.
Anticancer Res ; 41(4): 1831-1840, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813388

RESUMO

BACKGROUND/AIM: Peroxiredoxin V (Prx V) plays crucial roles in cellular apoptosis and proliferation in various cancer cells by regulating the cellular reactive oxygen species (ROS) levels. MATERIALS AND METHODS: Here, we examined the possible regulatory effects of Prx V on doxorubicin (DOX)-induced cellular apoptosis and its mechanisms in the human gastric adenocarcinoma cell line (AGS cells). RESULTS: Our findings suggest that Prx V knockdown may significantly increase the DOX-induced apoptosis by aggravating intracellular ROS accumulation. We also found that DOX-induced mitochondrial ROS levels and membrane permeability were significantly higher in short hairpin Prx V cells than in mock cells, and these phenomena were dramatically reversed by ROS scavenger treatment. Prx V knockdown also significantly upregulated the cleaved caspase 9, 3, and B-cell lymphoma 2 (Bcl2)-associated agonist of cell death/Bcl2 protein expression levels, suggesting that Prx V knockdown activates mitochondria-dependent apoptotic signaling pathways. CONCLUSION: Taken together, this study suggests that Prx V may be a strong molecular target for gastric cancer (GC) chemotherapy, and further elucidates the role of Prx V in oxidative stress-induced cell apoptosis.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Inativação Gênica , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxirredoxinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Peroxirredoxinas/genética , Transdução de Sinais , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
4.
In Vivo ; 35(1): 249-257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33402471

RESUMO

BACKGROUND/AIM: Curcumin is a polyphenol that exerts a variety of pharmacological activities and plays an anti-cancer role in many cancer cells. It was recently reported that gasdermin E (GSDME) is involved in the progression of pyroptosis. MATERIALS AND METHODS: HepG2 cells were treated with various concentrations of curcumin and cell viability was examined using MTT assay, apoptosis was analysed using flow cytometry, reactive oxygen species (ROS) levels using dihydroethidium, LDH release using an LDH cytotoxicity assay, and protein expression using western blot. RESULTS: Curcumin increased the expression of the GSDME N-terminus and proteins involved in pyrolysis, promoted HspG2 cell pyrolysis and increased intracellular ROS levels. Moreover, inhibition of the production of intracellular ROS with n-acetylcysteine (NAC) improved the degree of apoptosis and pyrolysis induced by curcumin. CONCLUSION: Curcumin induces HspG2 cell death by increasing apoptosis and pyroptosis, and ROS play a key role in this process. This study improves our understanding of the potential anti-cancer properties of curcumin in liver cancer.


Assuntos
Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Curcumina/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Piroptose , Espécies Reativas de Oxigênio
5.
Exp Ther Med ; 20(5): 82, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32968439

RESUMO

The aim of the present study was to verify the pro-apoptotic anticancer potential of several 5,8-dimethoxy-1,4-phthoquinone (DMNQ) derivatives in Ras-mediated tumorigenesis. MTT assays were used to detect cellular viability and flow cytometry was performed to assess intracellular reactive oxygen species (ROS) levels and apoptosis. The expression levels of proteins were detected via western blotting. Among the 12 newly synthesized DMNQ derivatives, 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione (BZNQ; component #1) significantly reduced cell viability both in mouse NIH3T3 embryonic fibroblasts cells (NC) and H-RasG12V transfected mouse NIH3T3 embryonic fibroblasts cells (NR). Moreover, BZNQ resulted in increased cytotoxic sensitivity in Ras-mutant transfected cells. Furthermore, the reactive oxygen species (ROS) levels in H-RasG12V transfected HepG2 liver cancer cells (HR) were significantly higher compared with the levels in HepG2 liver cancer cells (HC) following BZNQ treatment, which further resulted in increased cellular apoptosis. Eliminating cellular ROS using an ROS scavenger N-acetyl-L-cysteine markedly reversed BZNQ-induced cellular ROS accumulation and cell apoptosis in HC and HR cells. Western blotting results revealed that BZNQ significantly downregulated H-Ras protein expression and inhibited the Ras-mediated downstream signaling pathways such as protein kinase B, extracellular signal-related kinase and glycogen synthase kinase phosphorylation and ß-catenin protein expression. These results indicated that the novel DMNQ derivative BZNQ may be a therapeutic drug for Ras-mediated liver tumorigenesis. The results of the current study suggest that BZNQ exerts its effect by downregulating H-Ras protein expression and Ras-mediated signaling pathways.

6.
Oncol Lett ; 20(4): 103, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32831922

RESUMO

Over the past decade, a number of studies have demonstrated the resistance of cancer cells to conventional drugs and have recognized this as a major challenge in cancer therapy. While attempting to understand the underlying mechanisms of chemoresistance, several studies have suggested that the presence of cancer stem cells (CSCs) in tumors is one of the major pathways contributing toward resistance. Chemoresistance leads to cancer treatment failure and worsens the prognosis of patients. Natural herbal compounds are gaining attention as an alternative treatment strategy for cancer. These compounds may be effective against chemoresistant cells either alone or synergistically alongside conventional drugs, sensitizing cancer cells and enhancing the therapeutic efficacy. BRM270 is a natural compound made from seven herbal plant (Saururus chinensis, Citrus unshiu Markovich, Aloe vera, Arnebia euchroma, Portulaca oleracea, Prunella vulgaris var. lilacina and Scutellaria bacicalensis) extracts used in Asian traditional medicine and has the potential to target CSCs. Several studies have demonstrated the positive effects of BRM270 against chemoresistant cancer and its synergy alongside existing cancer drugs, including paclitaxel and gefitinib. These effects have been observed against various cancer types, including resistant non-small cell lung cancer (NSCLC), glioblastoma, multi-drug resistant osteosarcoma, cervical cancer, pancreatic cancer and hepatocarcinoma. The present review discusses the effects of BRM270 treatment against CSC-associated chemoresistance in common types of cancer.

7.
Biochem Biophys Res Commun ; 529(3): 635-641, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32736685

RESUMO

Keratinocyte hyperproliferation is an essential link in skin cancer pathogenesis. Peroxiredoxin I (Prx I) is known to regulate cancer cell proliferation, differentiation, and apoptosis, but its role in skin cancer remains unclear. This study aimed to elucidate the role and mechanism of Prx I in skin cancer pathogenesis. Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were used to create a skin tumor model of the initiation/promotion stage of cancer. The role of Prx I in H2O2-induced keratinocyte apoptosis was also investigated. After DMBA/TPA treatment, Prx I deficiency was significantly associated with less skin tumors, lower Bcl-2 expression, and higher p-p38 and cleaved caspase-3 expressions in Prx I knockout tumors than in wild-type controls. H2O2 stimulation caused more cellular apoptosis in Prx I knockdown HaCaT cells than in normal HaCaT cells. The signaling study revealed that Bcl-2, p-p38, and cleaved caspase-3 expressions were consistent with the results in the tumors. In conclusion, the deletion of Prx I triggered the DMBA/TPA-induced skin tumor formation in vivo and in vitro by regulating the reactive oxygen species (ROS)-p38 mitogen-activated protein kinase (MAPK) pathway. These findings provide a theoretical basis for treating skin cancer.


Assuntos
Apoptose/genética , Queratinócitos/metabolismo , Peroxirredoxinas/genética , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Cutâneas/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Células HEK293 , Humanos , Peróxido de Hidrogênio/farmacologia , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Camundongos da Linhagem 129 , Camundongos Knockout , Oxidantes/farmacologia , Peroxirredoxinas/deficiência , Interferência de RNA , Transdução de Sinais , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia
8.
Anticancer Res ; 40(8): 4491-4504, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727779

RESUMO

BACKGROUND: Peroxiredoxin II (PRDX2) performs unique roles in cells. It can reduce peroxides through cysteine residues, and helps prevent the effects of oxidative stress on cells. It is closely related to the occurrence and development of various diseases, especially alcoholic liver injury and even liver cancer. The metabolism of alcohol in hepatocytes leads to the increase in the levels of reactive oxygen species (ROS), oxidative stress, injury, and apoptosis. Therefore, this study focused on the investigating the protection conferred by PRDX2 against alcohol-induced apoptosis of hepatocytes. MATERIALS AND METHODS: PRDX2 inhibition of alcohol-induced apoptosis in L02 hepatocytes was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescence microscopy, flow cytometry, western blotting and hematoxylin and eosin staining. RESULTS: The results showed that the levels of reactive oxygen species, protein kinase B, ß-catenin, B-cell lymphoma-2 (BCL2), BCL-XL, BCL2-associated X, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase in PRDX2-silenced cells were increased significantly after the treatment of cells with ethanol. Similar results were obtained in an in vivo Prdx2-knockout mouse model of alcoholic liver injury. Therefore, PRDX2 may regulate the phosphorylation of the AKT signal protein by eliminating reactive oxygen species from cells, and it inhibits the downstream mitochondria-dependent apoptosis pathway, and, thereby, the apoptosis of cells. CONCLUSION: Thus, PRDX2 may be a potential molecular target for the prevention and treatment of alcoholic liver injury.


Assuntos
Etanol/efeitos adversos , Hepatócitos/citologia , Peroxirredoxinas/genética , Transdução de Sinais , Apoptose , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Fosforilação/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , beta Catenina/metabolismo
9.
Mol Med Rep ; 22(3): 1831-1838, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32705184

RESUMO

Apoptosis of pancreatic ß­cells is involved in the pathogenesis of type I and II diabetes. Peroxiredoxin I (Prx I) serves an important role in regulating cellular apoptosis; however, the role of Prx I in pancreatic ß­cell apoptosis is not completely understood. In the present study, the role of peroxiredoxin 1 (Prx I) during streptozotocin (STZ)­induced apoptosis of pancreatic ß­cells was investigated. The expression level of Prx I was decreased by STZ treatment in a time­dependent manner, and apoptosis of Prx I knockdown MIN6 cells was increased by STZ stimulation, compared with untransduced MIN6 cells. Furthermore, an intraperitoneal injection of STZ increased pancreatic islet damage in Prx I knockout mice, compared with wild­type and Prx II knockout mice. AKT and glycogen synthase kinase (GSK)­3ß phosphorylation significantly decreased following Prx I knockdown in MIN6 cells. However, phosphorylated ß­catenin and p65 levels significantly increased after STZ stimulation, compared with untransduced cells. The results of the present study indicate that deletion of Prx I mediated STZ­induced pancreatic ß­cell death in vivo and in vitro by regulating the AKT/GSK­3ß/ß­catenin signaling pathway, as well as NF­κB signaling. These findings provide a theoretical basis for treatment of pancreatic damage.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Regulação para Baixo , Células Secretoras de Insulina/citologia , Peroxirredoxinas/genética , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/efeitos adversos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo
10.
In Vivo ; 34(4): 1823-1833, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606152

RESUMO

BACKGROUND/AIM: Picrasma quassioides (P. quassioides) is used in traditional Asian medicine widely for the treatment of anemopyretic cold, eczema, nausea, loss of appetite, diabetes mellitus, hypertension etc. In this study we aimed to understand the effect of P. quassioides ethanol extract on SiHa cervical cancer cell apoptosis. MATERIALS AND METHODS: The P. quassioides extract-induced apoptosis was analyzed using the MTT assay, fluorescence microscopy, flow cytometry and western blotting. RESULTS: P. quassioides extract induced cellular apoptosis by increasing the accumulation of cellular and mitochondrial reactive oxygen species (ROS) levels and inhibiting ATP synthesis. Pretreatment with N-Acetylcysteine (NAC), a classic antioxidant, decreased the intracellular ROS production and inhibited apoptosis. In addition, the P38 MAPK signaling pathway is a key in the apoptosis of SiHa cells induced by the P. quassioides extract. CONCLUSION: The P. quassioides extract exerts its anti-cancer properties on SiHa cells through ROS-mitochondria axis and P38 MAPK signaling. Our data provide a new insight for P. quassioides as a therapeutic strategy for cervical cancer treatment.


Assuntos
Picrasma , Neoplasias do Colo do Útero , Apoptose , Feminino , Humanos , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Picrasma/metabolismo , Espécies Reativas de Oxigênio , Transdução de Sinais , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética
11.
Anticancer Res ; 40(7): 3819-3830, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620621

RESUMO

BACKGROUND: Picrasma quassioides (PQ) is a traditional Asian herbal medicine with anti-tumor properties that can inhibit the viability of HepG2 liver cancer cells. H-Ras is often mutated in liver cancer, however, the effect of PQ treatment on H-Ras mutated liver cancer is unclear. This study aimed to investigate the role of PQ on ROS accumulation and mitochondrial dysfunction in H-ras mutated HepG2 (HepG2G12V) cells. MATERIALS AND METHODS: PQ ethanol extract-induced HepG2G12V apoptosis was analyzed by the MTT assay, fluorescence microscopy, flow cytometry and western blotting. RESULTS: PQ treatment affected cell migration and colony formation in HepG2G12V cells. Cleaved-caspase-3, cleaved-caspase-9 and BCL2 associated agonist of cell death (BAD) expression levels were increased, while the levels of B-cell lymphoma-extra large (Bcl-xL) were decreased with PQ treatment. PQ treatment led to a reduction of H-Ras expression levels in liver cancer cells, thus reducing their abnormal proliferation. Furthermore, it led to increased expression levels of Peroxiredoxin VI, which regulates the redox signal in cells. CONCLUSION: Taken together these results provide a new functional significance for the role of PQ in treating HepG2G12V liver cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Mitocôndrias Hepáticas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Genes ras , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Picrasma/química , Proteínas Proto-Oncogênicas p21(ras)/biossíntese
12.
In Vivo ; 34(3): 1085-1094, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32354896

RESUMO

BACKGROUND/AIM: Cervical cancer is one of the leading causes of cancer death in women worldwide. BRM270 (BRMLife) has therapeutic potential for cancer treatment owing to its ability to inhibit cell proliferation, and expression of cluster of differentiation (CD) 133 in CD133+ cancer cells. This study was designed to evaluate the therapeutic effects of plant extract formulation BRM270 against cervical cancer progression. MATERIALS AND METHODS: The expression of sex-determining region Y-box 2 (SOX2) was tested in four different cervical cancer cell lines, HeLA, SiHa, Caski and C33A. SOX2-expressing SiHa and C33A cell lines were selected for further experiments on the in vitro and in vivo effects of BRM270 on cervical cancer progression using western blotting, flow cytometry, sphere-formation assay, magnetic-activated cell sorting of CD133+ cervical cancer cells, and xenografts in female athymic BALB/c nude mice. RESULTS: In the present study, in cervical cancer stem cells (CSCs), we found that BRM270 inhibited expression of SOX2, which is associated with cervical cancer initiation and metastasis. BRM270 also inhibited CD133 expression and induced apoptosis of CSCs and suppressed CD133+ CSC proliferation and sphere formation in vitro as well as SiHa and C33A cell xenograft tumor growth in vivo. This was accompanied by down-regulation of markers of epithelial-to-mesenchymal transition. CONCLUSION: BRM270 might be an effective agent for cervical cancer treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição SOXB1/antagonistas & inibidores , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Camundongos , Células-Tronco Neoplásicas/patologia , Neoplasias do Colo do Útero/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
In Vivo ; 34(3): 1077-1084, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32354895

RESUMO

Backgorund/Aim: Wogonin, a flavonoid-like compound extracted from the root of Scutellaria baicalensis Georgi, has been shown to have anticancer effects against cancer cells. Osteosarcoma is the most malignant type of bone cancer and can appear in any bone, with a high propensity for relapse and metastasis. The present study aimed to assess the anticancer effects of wogonin on osteosarcoma stem cells. MATERIALS AND METHODS: The cytotoxic effects of wogonin on CD133+ Cal72 osteosarcoma stem cells were assessed through in vitro experiments by MTT assay, transwell assay, sphere-formation assay, flow cytometry, immunocytochemistry and western blotting. RESULTS: Wogonin suppressed stem cell characteristics and the expression of stem cell-related genes by regulating reactive oxygen species (ROS) levels and ROS-related signaling of CD133+ Cal72 cells, effects which were reversed by ROS scavenger N-acetylcysteine. CONCLUSION: Wogonin may be a promising candidate for successful clinical management of osteosarcoma by regulating ROS-related mechanisms and stem cell-related genes.


Assuntos
Neoplasias Ósseas/metabolismo , Flavanonas/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Osteossarcoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Flavanonas/química , Humanos
14.
In Vivo ; 34(1): 133-141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882472

RESUMO

BACKGROUND/AIM: Dermal mesenchymal stem cells (DMSCs) are pluripotent stem cells found in the skin which maintain the thickness of the dermal layer and participate in skin wound healing. MATERIALS AND METHODS: The MTT assay was performed to detect cell proliferation and cell-cycle progression and cell-surface markers were assessed by flow cytometry. The levels of proteins in related signaling pathways were detected by western blotting assay and the translocation of ß-catenin into the nucleus were detected by immunofluorescence. Red oil O staining was performed to examine the differentiational ability of DMSCs. RESULTS: Knockout of PRDX2 inhibited DMSC cell growth, and cell-cycle arrest at G0/G1 phase; p16, p21 and cyclin D1 expression levels in Prdx2 knockout DMSCs were significantly increased. Furthermore, AKT phosphorylation were significantly increased in Prdx2 knockout DMSCs, GSK3ß activity were inhibited, result in ß-Catenin accumulated in the nucleus. CONCLUSION: In conclusion, these results demonstrated that PRDX2 plays a pivotal role in regulating the proliferation of DMSCs, and this is closely related to the AKT/glycogen synthase kinase 3 beta/ß-catenin signaling pathway.


Assuntos
Pontos de Checagem do Ciclo Celular/genética , Proliferação de Células/genética , Fase G1/genética , Células-Tronco Mesenquimais/patologia , Peroxirredoxinas/genética , Fase de Repouso do Ciclo Celular/genética , Transdução de Sinais/genética , Animais , Apoptose/genética , Linhagem Celular , Glicogênio Sintase Quinase 3 beta/genética , Camundongos , Camundongos Knockout , Fosforilação/genética , Proteínas Proto-Oncogênicas c-akt/genética , beta Catenina/genética
15.
In Vivo ; 34(1): 143-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882473

RESUMO

BACKGROUND/AIM: Numerous studies on various cancer cell lines have reported that direct exposure to non-thermal plasma treatment using plasma-activated medium (PAM) can be applied as a novel technology for cancer therapy. In this study, we investigated the inhibitory effects of PAM on Aspc1 pancreatic cancer cells and the mechanisms responsible for the cell death observed. MATERIALS AND METHODS: A colony-formation, sphere-formation, wound-healing and transwell assays, immunocytochemistry and western blot analysis were used monitor effects of PAM. RESULTS: PAM induced a greater cytotoxic effect in pancreatic cancer cells compared to that induced in NIH3T3 cells and 293T cells, and significantly inhibited colony and sphere formation, and cell migration of Aspc1 cells. Furthermore, PAM treatment increased the accumulation of reactive oxygen species (ROS) and reduced the mitochondrial membrane potential in Aspc1 cells. In addition, PAM treatment down-regulated the AKT serine/threonine kinase 1/signal transducer and activator of transcription 3 signaling pathway and induced ROS-dependent cellular autophagy. CONCLUSION: Our findings suggest that PAM can induce apoptosis of Aspc1 cells through ROS-dependent autophagy and may be a candidate for use in pancreatic cancer therapeutics.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células HEK293 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo
16.
Antioxidants (Basel) ; 9(1)2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31861323

RESUMO

Excessive alcohol intake can significantly reduce cognitive function and cause irreversible learning and memory disorders. The brain is particularly vulnerable to alcohol-induced ROS damage; the hippocampus is one of the most sensitive areas of the brain for alcohol neurotoxicity. In the present study, we observed significant increasing of intracellular ROS accumulations in Peroxiredoxin II (Prx II) knockdown HT22 cells, which were induced by alcohol treatments. We also found that the level of ROS in mitochondrial was also increased, resulting in a decrease in the mitochondrial membrane potential. The phosphorylation of GSK3ß (Ser9) and anti-apoptotic protein Bcl2 expression levels were significantly downregulated in Prx II knockdown HT22 cells, which suggests that Prx II knockdown HT22 cells were more susceptible to alcohol-induced apoptosis. Scavenging the alcohol-induced ROS with NAC significantly decreased the intracellular ROS levels, as well as the phosphorylation level of GSK3ß in Prx II knockdown HT22 cells. Moreover, NAC treatment also dramatically restored the mitochondrial membrane potential and the cellular apoptosis in Prx II knockdown HT22 cells. Our findings suggest that Prx II plays a crucial role in alcohol-induced neuronal cell apoptosis by regulating the cellular ROS levels, especially through regulating the ROS-dependent mitochondrial membrane potential. Consequently, Prx II may be a therapeutic target molecule for alcohol-induced neuronal cell death, which is closely related to ROS-dependent mitochondria dysfunction.

17.
Anticancer Res ; 39(11): 6115-6123, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704839

RESUMO

BACKGROUND/AIM: Colon cancer is the second most common deadliest malignancy in the world and better understanding of its underlying mechanisms is needed to improve clinical management. Natural plant extracts are gaining attention in the development of new therapeutic strategies against various cancer types. Shikonin is a naturally extracted naphthoquinone pigment with effects against cancer, including colon cancer. MATERIALS AND METHODS: In this study, we conducted a series of in vitro experiments to show the effects of Shikonin on colon cancer cell apoptosis. A colon cancer cell line with overexpression of peroxiredoxin V (PrxV) was constructed and the relationship of PrxV expression with Shikonin-induced cell apoptosis was investigated. RESULTS: Shikonin induced colon cancer cell apoptosis via regulation of mammalian target of rapamycin signaling. Shikonin-induced cell apoptosis was abrogated by overexpression of PrxV. CONCLUSION: According to the results obtained in this study, targeting PrxV may provide new insight for the successful management of colon cancer by inducing cell apoptosis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Naftoquinonas/farmacologia , Peroxirredoxinas/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Humanos , Células Tumorais Cultivadas
18.
In Vivo ; 33(4): 1183-1192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280208

RESUMO

BACKGROUND/AIM: Peroxiredoxin (Prx) protein family is aberrantly expressed in various cancers including gastric cancer. Among the six family members, Prx V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS) and modulates cellular apoptosis. This study aimed at investigating the role of Prx V in apoptosis of gastric cancer cells. MATERIALS AND METHODS: Stably constructed Prx V knockdown, over-expression and mock AGS cells (a human gastric adenocarcinoma cell line) were used to study the effect of Prx V on emodin-induced apoptosis by western blotting, cell viability, apoptosis and ROS detection assays. RESULTS: Overexpression of Prx V significantly decreased emodin-induced cellular apoptosis and ROS levels compared to Mock and Prx V knockdown AGS cells. Also, overexpression of Prx V down-regulated the expression of pro-apoptotic proteins, Bad and cleaved PARP, and increased the expression of anti-apoptotic protein, Bcl2. CONCLUSION: Prx V suppresses AGS cell apoptosis via scavenging intracellular ROS and modulating apoptosis-related markers.


Assuntos
Apoptose/efeitos dos fármacos , Apoptose/genética , Emodina/farmacologia , Peroxirredoxinas/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Imunofluorescência , Expressão Gênica , Humanos , Peroxirredoxinas/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo
19.
Anticancer Res ; 39(7): 3677-3686, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262894

RESUMO

BACKGROUND/AIM: Peroxiredoxin (Prx) V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS). Also, Prx V has been shown to mediate cell apoptosis in various cancers. However, the mechanism of Prx V-induced apoptosis in colon cancer cells remains unknown. Thus, in this study we analyzed the effects of Prx V in ß-lapachone-induced apoptosis in SW480 human colon cancer cells. MATERIALS AND METHODS: ß-lapachone-induced apoptosis was analyzed by the MTT assay, western blotting, fluorescence microscopy, Annexin V staining and flow cytometry. RESULTS: Overexpression of Prx V, significantly decreased ß-lapachone-induced cellular apoptosis and Prx V silencing increased ß-lapachone-induced cellular apoptosis via modulating ROS scavenging activity compared to mock SW480 cells. In addition, to further explore the mechanism of Prx V regulated ß-lapachone-induced SW480 cells apoptosis, the Wnt/ß-catenin signaling was studied. The Wnt/ ß-catenin signaling pathway was found to be induced by ß-lapachone. CONCLUSION: Prx V regulates SW480 cell apoptosis via scavenging ROS cellular levels and mediating the Wnt/ß-catenin signaling pathway, which was induced by ß-lapachone.


Assuntos
Apoptose , Neoplasias do Colo/metabolismo , Naftoquinonas , Peroxirredoxinas/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Via de Sinalização Wnt , Linhagem Celular Tumoral , Colo/metabolismo , Humanos
20.
Int J Mol Sci ; 20(11)2019 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-31159489

RESUMO

Alcoholic liver disease (ALD) refers to the damages to the liver and its functions due to alcohol overconsumption. It consists of fatty liver/steatosis, alcoholic hepatitis, steatohepatitis, chronic hepatitis with liver fibrosis or cirrhosis, and hepatocellular carcinoma. However, the mechanisms behind the pathogenesis of alcoholic liver disease are extremely complicated due to the involvement of immune cells, adipose tissues, and genetic diversity. Clinically, the diagnosis of ALD is not yet well developed. Therefore, the number of patients in advanced stages has increased due to the failure of proper early detection and treatment. At present, abstinence and nutritional therapy remain the conventional therapeutic interventions for ALD. Moreover, the therapies which target the TNF receptor superfamily, hormones, antioxidant signals, and MicroRNAs are used as treatments for ALD. In particular, mesenchymal stem cells (MSCs) are gaining attention as a potential therapeutic target of ALD. Therefore, in this review, we have summarized the current understandings of the pathogenesis and diagnosis of ALD. Moreover, we also discuss the various existing treatment strategies while focusing on promising therapeutic approaches for ALD.


Assuntos
Hepatopatias Alcoólicas/diagnóstico , Hepatopatias Alcoólicas/terapia , Animais , Gerenciamento Clínico , Diagnóstico Precoce , Humanos , Fígado/patologia , Hepatopatias Alcoólicas/patologia , Transplante de Fígado , Terapia de Alvo Molecular
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