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1.
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.

2.
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
3.
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
4.
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
5.
In Vivo ; 33(4): 999-1010, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31280188

RESUMO

Infrastructure in animal husbandry refers to fundamental facilities and services necessary for better living conditions of animals and its economy to function through better productivity. Mainly, infrastructure can be divided into two categories: hard infrastructure and soft infrastructure. Physical infrastructure, such as buildings, roads, and water supplying systems, belongs to hard infrastructure. Soft infrastructure includes services which are required to maintain economic, health, cultural and social standards of animal husbandry. Therefore, the proper management of infrastructure in animal husbandry is necessary for animal welfare and its economy. Among various technologies to improve the quality of infrastructure, non-thermal plasma (NTP) technology is an effectively applicable technology in different stages of animal husbandry. NTP is mainly helpful in maintaining better health conditions of animals in several ways via decontamination from microorganisms present in air, water, food, instruments and surfaces of animal farming systems. Furthermore, NTP is used in the treatment of waste water, vaccine production, wound healing in animals, odor-free ventilation, and packaging of animal food or animal products. This review summarizes the recent studies of NTP which can be related to the infrastructure in animal husbandry.


Assuntos
Criação de Animais Domésticos , Gases em Plasma , Poluição do Ar , Ração Animal , Bem-Estar do Animal , Animais , Animais Domésticos , Ambiente Controlado , Água/análise , Água/química , Microbiologia da Água
6.
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
7.
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
8.
Sci Rep ; 9(1): 8865, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222092

RESUMO

The sperm quality is a vital economical requisite of poultry production. Our previous study found non-thermal dielectric barrier discharge plasma exposure on fertilized eggs could increase the chicken growth and the male reproduction. However, it is unclear how plasma treatment regulates the reproductive capacity in male chickens. In this study, we used the optimal plasma treatment condition (2.81 W for 2 min) which has been applied on 3.5-day-incubated fertilized eggs in the previous work and investigated the reproductive performance in male chickens aged at 20 and 40 weeks. The results showed that plasma exposure increased sperm count, motility, fertility rate, and fertilization period of male chickens. The sperm quality-promoting effect of plasma treatment was regulated by the significant improvements of adenosine triphosphate production and testosterone level, and by the modulation of reactive oxygen species balance and adenosine monophosphate-activated protein kinase and mammalian target of rapamycin pathway in the spermatozoa. Additionally, the plasma effect suggested that DNA demethylation and microRNA differential expression (a total number of 39 microRNAs were up-regulated whereas 53 microRNAs down-regulated in the testis) regulated the increases of adenosine triphosphate synthesis and testosterone level for promoting the chicken sperm quality. This finding might be beneficial to elevate the fertilization rate and embryo quality for the next generation in poultry breeding.


Assuntos
Galinhas , MicroRNAs/genética , Espermatozoides/citologia , Testículo/fisiologia , Trifosfato de Adenosina/sangue , Animais , Masculino , Espécies Reativas de Oxigênio/sangue , Contagem de Espermatozoides , Motilidade Espermática , Testosterona/sangue
9.
Artigo em Inglês | MEDLINE | ID: mdl-31049070

RESUMO

Pancreatic cancer has a poor survival rate as compared to other types of cancer. Surface marker CD44 plays important role in epithelial-mesenchymal transition and cancer stem cell phenotype. Therefore, targeting CD44 positive pancreatic cancer cells might enhance therapies effectiveness. Our previous studies indicated the antitumorigenesis effect of BRM270 in osteosarcoma, lung cancer, and glioblastoma; however there is no evidence on BRM270 impacts on pancreatic cancer growth. In this study, we investigated the effect of BRM270 on the isolated CD44 positive pancreatic ductal adenocarcinoma cells (CD44+ PDAC). Results showed that CD44 positive cells undergo apoptosis induced by BRM270. Moreover, BRM270 also inhibits stemness and metastasis traits in CD44+ PDAC via Sonic hedgehog signaling pathway and SALL4 expression. In vivo study indicated that tumor growth derived from CD44+ PDAC was suppressed as daily uptake by BRM270 5 mg/kg. These data suggest the alternative approach in antipancreatic tumorigenesis via herbal plants extract and selectively targeting CD44+ PDAC cells in tumor.

10.
In Vivo ; 33(3): 749-755, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028193

RESUMO

BACKGROUND/AIM: Staphylococcus aureus (S. aureus) is a major gram-positive pathogen, which can cause toxic and immunogenic injuries both in nosocomial and community-acquired infections. Peroxiredoxin (Prx) I plays crucial roles in cellular apoptosis, proliferation, and signal transduction as well as in immunoregulation. The present study aimed to investigate whether Prx I protects mice from death caused by the heat-killed Staphylococcus aureus. MATERIALS AND METHODS: In the present study, we challenged the wild-type and Prx I-deficient mice with heat-killed S. aureus (HKSA). The effects of Prx I were evaluated by a series of in vitro and in vivo experiments including western blot, Haematoxylin and Eosin staining, splenocyte analysis and cytokines analysis. RESULTS: Intra-peritoneal (ip) inoculation of HKSA resulted in increased mortality of Prx I-knockout (KO) mice with severe liver damage and highly populated spleens with lymphocytes. Furthermore, HKSA infections also bursted the production of both pro-inflammatory and anti-inflammatory serum cytokines in Prx I KO compared to wild-type mice. CONCLUSION: Enhanced mortality of S. aureus-infected mice with Prx I deficiency suggested that Prx I may protect against the infection-associated lethality of mice.


Assuntos
Peroxirredoxinas/imunologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia , Animais , Apoptose , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Camundongos , Mortalidade , Peroxirredoxinas/genética , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/genética
11.
Mater Sci Eng C Mater Biol Appl ; 97: 166-176, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30678901

RESUMO

BRM270 is the most leading phytochemical extract that possesses potent anticancer properties. A major challenge associated with this drug is its low bioavailability and thus requires high dosages for cancer treatment. Here, we report the novel nano-synthesis of phyto-composite, BRM270 for the first time by mechanical milling method with specific modifications for enhanced cytotoxicity against HepG2 human hepatoma cancer cells. Unlike free BRM270 and other phytomedicines, BRM270 nanoparticles (BRM270 NPs) are well-dispersed and small sized (23 to 70 nm) which is believed to greatly enhanced cellular uptake. Furthermore, the acidic tumor microenvironment attracts BRM270 NPs enhancing targeted therapy while leaving normal cells less affected. The comparative cytotoxicity analysis using MTT assay among the three treatment groups, such as free BRM270, BRM270 NPs, and doxorubicin demonstrated that BRM270 NPs induced greater cytotoxicity against HepG2 cells with an effective drug concentration of 12 µg/ml. From FACS analysis, we observed an apoptotic cell death of 44.4% at BRM270 NPs treated cells while only 12.5% found in the free BRM270 treated cells. Further, the comparative relative expression profiling of the candidate genes were showed significant (p < 0.05) down-regulation of IL6, BCL2, p53, and MMP9 in the BRM270 NPs treated cells, compared to the free BRM270 and doxorubicin. Indeed, the genes, CASPASE 9 and BAX have shown significant (p < 0.05) upregulation in cells treated with BRM270 NPs as compared to counter treatment groups. The investigation of the signal pathways and protein-protein network associations were also carried out to elucidate the functional insights underlying anti-cancer potential of BRM270 NPs in HepG2 cells. Taken together, our findings demonstrated that these uniquely engineered BRM270 NPs effectively enter into the cancer cells due to its acidic microenvironment thereby inducing apoptosis and regulate the cell-proliferation in-vitro at extremely low dosages.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Nanopartículas/química , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Medicamentos de Ervas Chinesas/síntese química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Microscopia Eletrônica de Varredura , Reprodutibilidade dos Testes
12.
Infect Immun ; 87(3)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30559219

RESUMO

Gallibacterium anatis is a pathogen associated with peritonitis and salpingitis in chickens and other avian species. Novel safety prevention strategies are urgently needed because of widespread multidrug resistance and antigenic diversity. The objective of this study was to produce a specific chicken egg yolk antibody and evaluate its protective response against a G. anatis infection model in 4-week-old chicks. Enzyme-linked immunosorbent assays showed that hens immunized with the recombinant N terminus of Gallibacterium toxin A (GtxA-N) had significantly increased antibody titers against GtxA-N in serum and egg yolk IgY. Western blotting showed that IgY antibody had specificity against GtxA-N in the egg yolks of immunized hens. The growth of G. anatis in brain heart infusion (BHI) broth and agar was significantly inhibited by the GtxA-N-specific IgY antibody. The protective effects of the specific IgY antibody were evaluated in G. anatis-infected chicks after intramuscular injection (10 mg/ml). The anti-GtxA-N antibody titers in the sera of G. anatis-challenged chicks following an injection of specific IgY antibody were significantly higher than those of the control and the nonspecific IgY groups, but lower lesion scores for the peritoneum, liver, and duodenum were found after specific IgY antibody treatment. The results from this study suggest that the GtxA-N-specific IgY antibody could potentially improve the protective response against G. anatis infection in chicks.


Assuntos
Anticorpos Antibacterianos/imunologia , Infecções Bacterianas/prevenção & controle , Galinhas/imunologia , Gema de Ovo , Gammaproteobacteria/imunologia , Animais , Feminino , Imunoglobulinas/imunologia
13.
Cancer Gene Ther ; 26(9-10): 292-304, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30341415

RESUMO

Previously, we demonstrated that Prx II is important for survival of the gefitinib-resistant A549 (A549/GR) cell line, an NSCLC cell line derived by repeated exposure to gefitinib. Therefore, in this study, we used A549/GR cells to investigate the role of Prx II in GR NSCLC stemness. Initially, to explore the stemness characteristics and investigate the association of Prx II with those stemness characteristics, we successfully isolated a stem cell-like population from A549/GR cells. A549/GR CD133+ cells possessed important cancer stemness characteristics, including the abilities to undergo metastasis, angiogenesis, self-renewal, and to express stemness genes and epithelial-mesenchymal transition (EMT) markers. However, those characteristics were abolished by knocking down Prx II expression. MicroRNA 122 (miR-122) targets Prx II in A549/GR cancer stem cells (CSCs), thereby inhibiting the stemness characteristics in vitro and in vivo. Next, we investigate whether miR-122 overexpression was associated with Prx II expression and Prx-II-induced stemness characteristics, we transfected miR-122 into A549/GR CSCs. MiR-122 inhibited A549/GR stemness by downregulating the Hedgehog, Notch, and Wnt/ß-catenin pathways. Taken together, our data suggest that Prx II promotes A549/GR stemness, and that targeting Prx II and miR-122 is a potentially viable strategy for anti-cancer-stem cell therapy in GR NSCLCs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Gefitinibe/farmacologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Peroxirredoxinas/genética , Antígeno AC133/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos/genética , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Interferência de RNA , Receptores Notch/metabolismo , Via de Sinalização Wnt
14.
Cancers (Basel) ; 10(9)2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30177619

RESUMO

Cancer stem cells (CSCs) represent a sub-population of cancer cells with the ability to regulate stemness-associated properties which are specifically responsible for unlimited growth of cancers, generation of diverse cancer cells in differentiated state and resistance to existing chemotherapy and radiotherapy. Even though, current therapies destroy majority of cancer cells, it is believed to leave CSCs without eradicating which may be the conceptualization for chemoresistance and radio-resistance. Reactive oxygen species (ROS) maintain stem cells and regulate the stemness-associated properties of cancers. Beyond the maximum limit, ROS can damage cellular functions of cancers by subjecting them to oxidative stress. Thus, maintenance of ROS level plays an important role in cancers to regulate stemness-associated properties. Peroxiredoxin II (Prx II) is a member of peroxiredoxin antioxidant enzyme family which considers as a regulator of ROS in cellular environments by modulating redox status to maintain CSC phenotype and stemness properties. Prx II has cell type-dependent expression in various types of cancer cells and overexpression or silenced expression of Prx II in cancers is associated with stem cell phenotype and stemness-associated properties via activation or deactivation of various signaling pathways. In this review, we summarized available studies on Prx II expression in cancers and the mechanisms by which Prx II takes parts to regulate CSCs and stemness-associated properties. We further discussed the potential therapeutic effects of altering Prx II expression in cancers for better anticancer strategies by sensitizing cancer cells and stem cells to oxidative stress and inhibiting stemness-associated properties.

15.
Artigo em Inglês | MEDLINE | ID: mdl-30154906

RESUMO

Inflammation is tightly associated with carcinogenesis at both the initiation and development of tumor. Many reports indicated that Cox-2 substantially contributes to inflammation and tumorigenesis. The novel nutraceutical KJS018A (BRM270 Function Enhanced Products) is the extract mixture from 8 herbal plants, which have been used to inhibit cancers and inflammation. The aim of the present study is to examine the inhibitory effects of KJS018A mixture to hepatocarcinogenesis and inflammation. The results showed that KJS018A significantly inhibited the proliferation of hepatic malignant cells and downregulated levels of IL-6 and Cox-2. Furthermore, KJS018A diminished the effect of PMA, an inflammatory inducer via IL-6/STAT3/Cox-2 pathway. Furthermore, KJS018A suppressed metastatic traits of hepatic malignant cells via downregulating Twist, N-cadherin, and MMP-9 while restoring E-cadherin expression. KJS018A also restrained tumor growth and levels of IL-6 and Cox-2 in immunohistochemistry staining. Taken together, these data suggest potential application of KJS018A in prevention of hepatocarcinogenesis promoted by inflammation.

16.
Int J Mol Sci ; 19(8)2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30082605

RESUMO

As an innovative technology in biological applications-non-thermal plasma technique-has recently been applied to living cells and tissues. However, it is unclear whether non-thermal plasma treatment can directly regulate the growth and development of livestock. In this study, we exposed four-day-incubated fertilized eggs to plasma at 11.7 kV for 2 min, which was found to be the optimal condition in respect of highest growth rate in chickens. Interestingly, plasma-treated male chickens conspicuously grew faster than females. Plasma treatment regulated the reactive oxygen species homeostasis by controlling the mitochondrial respiratory complex activity and up-regulating the antioxidant defense system. At the same time, growth metabolism was improved due to the increase of growth hormone and insulin-like growth factor 1 and their receptors expression, and the rise of thyroid hormones and adenosine triphosphate levels through the regulation of demethylation levels of growth and hormone biosynthesis-related genes in the skeletal muscles and thyroid glands. To our knowledge, this study was the first to evaluate the effects of a non-thermal plasma treatment on the growth rate of chickens. This safe strategy might be beneficial to the livestock industry.


Assuntos
Hormônios Tireóideos/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Galinhas , Hormônio do Crescimento/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Espécies Reativas de Oxigênio/metabolismo
17.
Anticancer Res ; 38(7): 3967-3975, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29970519

RESUMO

BACKGROUND/AIM: Natural products extracted from plants can be potent for developing pharmaceutical products. Hispidin, a polyphenolic compound mainly derived from the medicinal mushroom Phellinus linteus, has been shown to have a therapeutic potential against cancer cells. Pancreatic cancer is one of the most aggressive solid malignancies with high resistance to existing drugs. Cancer stem cells (CSCs) are responsible for chemoresistance. The present study aimed to evaluate the anticancer effects of hispidin on pancreatic CSCs. MATERIALS AND METHODS: The cytotoxic effects of hispidin on BxPC-3 and AsPC-1 pancreatic cancer cells and BxPC-3 CD44+ CSCs and the synergistic effects of gemcitabine and hispidin on CSCs were evaluated by a series of in vitro experiments including the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), fluorescence-activated cell sorting, colony forming, Transwell assay, immunocytochemistry, sphere-forming, and western blot assays. RESULTS: Hispidin exerted antitumor effects against both BxPC-3 pancreatic cancer cells and CSCs. Furthermore, it was found that hispidin sensitized pancreatic CSCs to gemcitabine and promoted the therapeutic efficacy of gemcitabine. CONCLUSION: Hispidin might be a novel chemosensitizer for gemcitabine and a potential synergistic agent for increasing the therapeutic index of gemcitabine as a treatment for pancreatic cancer.


Assuntos
Desoxicitidina/análogos & derivados , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Pancreáticas/patologia , Pironas/farmacologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Humanos , Pironas/administração & dosagem
18.
Biochem Biophys Res Commun ; 503(4): 2248-2254, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-29958885

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a major malignant phenotype in pancreatic cancer, which is one of the most death causes by cancer in the world. PDAC developed from pancreatic intra-epithelial neoplasms (PanINs) and poorly diagnosed at early stages. Beside of high drug resistance, metastasis is the great concern during pancreatic cancer treatment. SALL4 expression is inherent in the upregulations of endothelial mesenchymal transition (EMT) genes and therefore promoting cancer metastasis. Furthermore, some of evidences indicated reactive oxygen species (ROS) is also influent to metastasis and self-antioxidant capacity seems a gold standard for successful metastasis rate. In this study, we have found the role Spalt like protein 4 (SALL4) to PDAC proliferation, mobility and its regulation to mitochondrial ROS via FoxM1/Prx III axis. It is possible that SALL4 mainly induces endothelial-mesenchymal transition (EMT) phenotype and favors ROS loss to facilitate metastasis efficiency in PDAC cells. Therefore, SALL4 might be a promising marker for PDAC treatment and targeting SALL4 would benefit anti-proliferative and anti-metastasis therapies.


Assuntos
Carcinoma Ductal Pancreático/metabolismo , Proteína Forkhead Box M1/metabolismo , Peroxirredoxina III/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Fatores de Transcrição/fisiologia , Movimento Celular , Proliferação de Células , Transdiferenciação Celular , Humanos , Metástase Neoplásica , Fenótipo
19.
Sci Rep ; 8(1): 8761, 2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29884805

RESUMO

Non-thermal plasma treatment is an emerging innovative technique with a wide range of biological applications. This study was conducted to investigate the effect of a non-thermal dielectric barrier discharge plasma technique on immature chicken Sertoli cell (SC) viability and the regulatory role of microRNA (miR)-7450. Results showed that plasma treatment increased SC apoptosis in a time- and dose-dependent manner. Plasma-induced SC apoptosis possibly resulted from the excess production of reactive oxygen species via the suppression of antioxidant defense systems and decreased cellular energy metabolism through the inhibition of adenosine triphosphate (ATP) release and respiratory enzyme activity in the mitochondria. In addition, plasma treatment downregulated miR-7450 expression and activated adenosine monophosphate-activated protein kinase α (AMPKα), which further inhibited mammalian target of rapamycin (mTOR) phosphorylation in SCs. A single-stranded synthetic miR-7450 antagomir disrupted mitochondrial membrane potential and decreased ATP level and mTOR phosphorylation by targeting the activation of AMPKα, which resulted in significant increases in SC lethality. A double-stranded synthetic miR-7450 agomir produced opposite effects on these parameters and ameliorated plasma-mediated apoptotic effects on SCs. Our findings suggest that miR-7450 is involved in the regulation of plasma-induced SC apoptosis through the activation of AMPKα and the further inhibition of mTOR signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Apoptose , Regulação da Expressão Gênica , MicroRNAs/genética , Gases em Plasma/farmacologia , Células de Sertoli/citologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Galinhas , Ativação Enzimática/efeitos dos fármacos , Desenho de Equipamento , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
20.
Sci Rep ; 8(1): 7576, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29765100

RESUMO

The quality of avian semen is an important economic trait in poultry production. The present study examines the in vitro effects of non-thermal dielectric barrier discharge plasma on chicken sperm to determine the plasma conditions that can produce the optimum sperm quality. Exposure to 11.7 kV of plasma for 20 s is found to produce maximum sperm motility by controlling the homeostasis of reactive oxygen species and boosting the release of adenosine triphosphate and respiratory enzyme activity in the mitochondria. However, prolonged exposure or further increase in plasma potential impairs the sperm quality in a time- and dose-dependent manner. Optimal plasma treatment of sperm results in upregulated mRNA and protein expression of antioxidant defense-related and energetic metabolism-related genes by increasing their demethylation levels. However, 27.6 kV of plasma exerts significant adverse effects. Thus, our findings indicate that appropriate plasma exposure conditions improve chicken sperm motility by regulating demethylation levels of genes involved in antioxidant defense and energetic metabolism.


Assuntos
Redes Reguladoras de Genes/efeitos dos fármacos , Gases em Plasma/farmacologia , Motilidade Espermática/efeitos dos fármacos , Espermatozoides/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Galinhas , Desmetilação , Relação Dose-Resposta a Droga , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/efeitos dos fármacos , Fatores de Tempo , Regulação para Cima
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