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1.
Biol Pharm Bull ; 41(9): 1440-1447, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30175778

RESUMO

The significant correlation between nasal symptom scores and level of histamine H1 receptor (H1R) mRNA in nasal mucosa was observed in patients with pollinosis, suggesting that H1R gene is an allergic disease sensitive gene. We demonstrated that H1R and interleukin (IL)-9 gene are the allergic rhinitis (AR)-sensitive genes and protein kinase Cδ (PKCδ) signaling and nuclear factor of activated T-cells (NFAT) signaling are involved in their expressions, respectively. Honey bee products have been used to treat allergic diseases. However, their pathological mechanism remains to be elucidated. In the present study, we investigated the mechanism of the anti-allergic effect of royal jelly (RJ) and Brazilian green propolis (BGPP). Treatment with RJ and BGPP decreased in the number of sneezing on toluene 2,4-diissocyanate (TDI)-stimulated rats. The remarkable suppression of H1R mRNA in nasal mucosa was observed. RJ and BGPP also suppressed the expression of IL-9 gene. RJ and BGPP suppressed phorbol-12-myristate-13-acetate-induced Tyr311 phosphorylation of PKCδ in HeLa cells. In RBL-2H3 cells, RJ and BGPP also suppressed NFAT-mediated IL-9 gene expression. These results suggest that RJ and BGPP improve allergic symptoms by suppressing PKCδ and NFAT signaling pathways, two important signal pathways for the AR pathogenesis, and suggest that RJ and BGPP could be good therapeutics against AR.


Assuntos
Citocinas/genética , Ácidos Graxos/farmacologia , Própole/farmacologia , Receptores Histamínicos H1/genética , Rinite Alérgica/genética , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Masculino , Fatores de Transcrição NFATC/metabolismo , Mucosa Nasal/metabolismo , Proteína Quinase C-delta/metabolismo , RNA Mensageiro/metabolismo , Ratos , Rinite Alérgica/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Tolueno 2,4-Di-Isocianato
2.
J Cell Biochem ; 117(3): 730-40, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26335446

RESUMO

Protein kinase C (PKC) is a family of serine/threonine kinases that regulate diverse cellular functions including cell death, proliferation, and survival. Recent studies have reported that PKCδ, are involved in apoptosis or autophagy induction. In the present study we focused on how PKCδ regulates proliferation and cancer stem cell (CSC) properties of the hormone-independent mammary cancer cell line LM38-LP, using pharmacological and genetic approaches. We found that pharmacological inhibition of PKCδ, by Rottlerin treatment, impairs in vitro LM38-LP proliferation through cell cycle arrest, inducing the formation of cytoplasmic-vacuoles. Using immunofluorescence we confirmed that Rottlerin treatment induced the apparition of LC3 dots in cell cytoplasm, and increased autophagy flux. On the other side, the same treatment increased CSC growth rate and self-renewal. Furthermore, Rottlerin pre-treatment induced in CSC the development of a "grape-like" morphology when they are growing in 3D cultures (Matrigel), usually associated with a malignant phenotype, as well as an increase in the number of experimental lung metastasis when these cells were inoculated in vivo. The PKCδ knockdown, by RNA interference, induced autophagy and increased CSC number, indicating that these effects are indeed exerted through a PKCδ dependent pathway. Finally, the increase in the number of mammospheres could be reversed by a 3MA treatment, suggesting that autophagy mechanism is necessary for the increased of CSC self-renewal induced by PKCδ inhibition. Here we demonstrated that PKCδ activity exerts a dual role through the autophagy mechanism, decreasing proliferative capacity of mammary tumor cells but also regulating tumor stem cell self-renewal.


Assuntos
Autofagia , Neoplasias Pulmonares/enzimologia , Neoplasias Mamárias Experimentais/enzimologia , Células-Tronco Neoplásicas/fisiologia , Proteína Quinase C-delta/metabolismo , Acetofenonas/farmacologia , Animais , Antineoplásicos/farmacologia , Benzopiranos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Autorrenovação Celular , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Pulmonares/secundário , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteína Homeobox Nanog/genética , Proteína Homeobox Nanog/metabolismo , Transplante de Neoplasias , Proteína Quinase C-delta/antagonistas & inibidores , Proteína Quinase C-delta/genética , Inibidores de Proteínas Quinases/farmacologia
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