RESUMO
Curcumin (cur) has been comprehensively studied for its various biological properties, more precisely for its antitumor potential and it has shown the promising results as well. On the other hand, Chlorin e6 (Ce6) has mostly been used as a photosensitizer in photodynamic therapy (PDT) against a variety of carcinomas. In the present study, we have synthesized a series of Chlorin e6-curcumin (Ce6-cur) conjugates and investigated their photosensitizing potential against pancreatic cancer cell lines. All the synthesized compounds were characterized by UV, 1H NMR, 13C NMR and LC-MS. These Ce6-cur conjugates showed better physicochemical properties and higher singlet oxygen generation capability. The cellular uptake was studied in AsPC-1â¯cells using fluorescence-activated cell sorting (FACS). Compound 17 was rapidly internalized within 30â¯min and sustained for 24â¯h. Compound 17 showed excellent PDT efficacy with IC50 of 40, 35 and 41â¯nM against AsPC-1, MIA PaCa-2 and PANC-1 respectively with exceptional dark/phototoxicity ratio in the range of 2371-7500. Moreover, the treatment of compound 17 upregulated the expression of BAX, Cytochrome-C and cleaved caspase 9 while downregulating the Bcl-2 expression an anti-apoptotic protein marker. These results demonstrate outstanding capability of compound 17 as a potent photosensitizer which could improve the PDT efficacy in pancreatic cancer patients.
Assuntos
Antineoplásicos/farmacologia , Curcumina/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Clorofilídeos , Curcumina/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Neoplasias Pancreáticas/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Relação Estrutura-Atividade , Neoplasias PancreáticasRESUMO
Bee venom (BV) therapy is a type of alternative medical treatment used to treat various diseases in oriental medicine. The mechanisms underlying the effects of BV remain poorly understood. In the present study, we evaluated the antiviral effect of BV on cervical carcinoma cell lines (CaSki, HeLa, C33A and TC-1). BV treatments resulted in a more significant suppression of cell growth in HPV 16-infected cells (CaSki) and a lesser suppression in HPV 18-infected cells (HeLa). However, less suppression was observed in HPV-negative C33A cells. In 10 µg/ml BV-treated CaSki cells, the mRNA expression and protein levels of HPV16 E6 and E7 were significantly decreased by BV, while HPV18 E6 and E7 mRNA expression levels were not significantly altered by 10 µg/ml BV-treated HeLa cells. The antitumor effects of BV were in accordance with in vitro data, in restricting tumor growth in vivo and were much more effective on the suppression of tumor growth. Furthermore, the mRNA and protein expression levels of HPV16 E6 and E7 were decreased by BV in TC-1 tumors. These findings demonstrated the antiviral effects of BV in HPV-infected cervical cancer cells and the anticancer effects of BV in HPV16 E6/E7-expressed TC-1 tumors. Collectively, BV plays a differential role in suppressing HPV16-infected cells (CaSki cells) and HPV18-infected cells (HeLa cells) by the downregulation of E6/E7 protein of HPV16/18.
Assuntos
Antineoplásicos/farmacologia , Antivirais/farmacologia , Venenos de Abelha/farmacologia , Terapia Biológica , Carcinoma de Células Escamosas/patologia , Proteínas de Ligação a DNA/biossíntese , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Papillomavirus Humano 16/efeitos dos fármacos , Papillomavirus Humano 18/efeitos dos fármacos , Proteínas de Neoplasias/biossíntese , Proteínas Oncogênicas Virais/biossíntese , Proteínas E7 de Papillomavirus/biossíntese , Infecções por Papillomavirus/patologia , Proteínas Repressoras/biossíntese , Neoplasias do Colo do Útero/patologia , Animais , Antineoplásicos/uso terapêutico , Venenos de Abelha/uso terapêutico , Carcinoma de Células Escamosas/virologia , Linhagem Celular Transformada/transplante , Linhagem Celular Tumoral , Transformação Celular Viral , Proteínas de Ligação a DNA/genética , Regulação para Baixo , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Genes ras , Células HeLa , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pulmão/citologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/genética , Neoplasias Experimentais/terapia , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/virologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Distribuição Aleatória , Proteínas Repressoras/genética , Neoplasias do Colo do Útero/virologiaRESUMO
The aim of this study was to determine serum selenium (Se) levels during the development of liver disease as well as the possible Se supplementation benefits in liver disease patients. Serum was collected from 187 patients with liver diseases and 120 normal healthy people living in Seoul. The samples were collected at the Kangnam St. Mary's Hospital College of Medicines, The Catholic University of Korea, in accordance with procedures approved by the Institutional Review Board of the Catholic University of Korea. Serum Se levels were quantified by inductively coupled plasma mass spectrometry and were compared between healthy and liver diseases patients. Se levels were 92.65 ± 32.50 µg/l in hepatitis infection, 92.33 ± 30.66 µg/l in hepatitis B virus infection and 96.41 ± 51.50 µg/l in hepatitis C virus infection, 96.42 ± 32.80 µg/l in cirrhosis, and 67.47 ± 14.30 µg/l in hepatoma patients. Findings were significantly lower in hepatitis and hepatoma as compared with the healthy participants (P < 0.001). The Se level of the healthy population was 108.38 ± 29.50, 119.37 ± 28.31 for males and 97.87 ± 26.99 µg/l for females. Our data shows the same parallelism between liver disease progression and decrease of Se levels except in the case of liver cirrhosis. And also, our study confirms the previous findings of significantly lower Se levels in Korean hepatoma patients. Se levels that decrease parallel to liver disease progression should be further integrated and analyzed with liver function blood biomarkers.