RESUMEN
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.
Asunto(s)
Antineoplásicos/farmacología , Antivirales/farmacología , Venenos de Abeja/farmacología , Terapia Biológica , Carcinoma de Células Escamosas/patología , Proteínas de Unión al ADN/biosíntesis , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Viral de la Expresión Génica/efectos de los fármacos , Papillomavirus Humano 16/efectos de los fármacos , Papillomavirus Humano 18/efectos de los fármacos , Proteínas de Neoplasias/biosíntesis , Proteínas Oncogénicas Virales/biosíntesis , Proteínas E7 de Papillomavirus/biosíntesis , Infecciones por Papillomavirus/patología , Proteínas Represoras/biosíntesis , Neoplasias del Cuello Uterino/patología , Animales , Antineoplásicos/uso terapéutico , Venenos de Abeja/uso terapéutico , Carcinoma de Células Escamosas/virología , Línea Celular Transformada/trasplante , Línea Celular Tumoral , Transformación Celular Viral , Proteínas de Unión al ADN/genética , Regulación hacia Abajo , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Genes ras , Células HeLa , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Pulmón/citología , Ratones , Ratones Endogámicos C57BL , Proteínas de Neoplasias/genética , Neoplasias Experimentales/terapia , Proteínas Oncogénicas Virales/genética , Proteínas E7 de Papillomavirus/genética , Infecciones por Papillomavirus/virología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Distribución Aleatoria , Proteínas Represoras/genética , Neoplasias del Cuello Uterino/virologíaRESUMEN
Selenium, an essential trace element possessing anti-carcinogenic properties, can induce apoptosis in cancer cells. Our goal was to investigate the enhanced antitumor effects of photodynamic therapy (PDT) plus selenium in TC-1 tumor cells and implanted mice. Cell viability was evaluated at various time intervals after PDT treatment and/or selenium by methyl thiazolyl tetrazolium (MTT) assay. When only PDT treatment was administered to TC-1 tumor cells, TC-1 cell growth recovered over time. On the other hand, co-treatment of PDT and selenium extended the inhibition time of tumor cell growth. Co-treatment of PDT and selenium showed serious morphological changes in TC-1 cells and induced a more apoptotic population by FACS analysis. By signal transduction pathway SuperArray analysis, genes closely involved in the NFκB, p53 and phopholipase C pathways, such as VCAM1, MDM2 and FOS, were significantly downregulated at least 10-fold in TC-1 cells following PDT and selenium cotreatment. In an in vivo study, tumor-bearing mice were intravenously injected with Radachlorin 3 h before irradiation with 300 J/cm2 of light. Selenium was administered daily for 20 days. Combination therapy against the mouse tumors generated by TC-1 cells was more effective than PDT or selenium alone. These data suggest that selenium plus PDT can induce a significant tumor suppression response compared with PDT alone. Additionally, it can be an effective anticancer therapy strategy.
Asunto(s)
Neoplasias Experimentales/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Porfirinas/farmacología , Selenio/farmacología , Animales , Procesos de Crecimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Femenino , Expresión Génica , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patologíaRESUMEN
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.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Selenio/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carcinoma Hepatocelular/epidemiología , Femenino , Hepatitis/sangre , Hepatitis/epidemiología , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/epidemiología , Masculino , Persona de Mediana Edad , República de Corea/epidemiologíaRESUMEN
Of trace elements in the serum of living organisms, selenium (Se) is an essential mineral and plays the role of an antioxidant as selenoproteins protecting the organism against oxidative damage induced by hydrogen peroxide, other lipid hydroperoxides, and their derivatives. The aim of this study was to determine the mean serum Se levels in healthy Korean volunteers (50 males and 50 females) by using an inductively coupled plasma-mass spectrometry method. The samples were collected at the Health Promotion Centre of Kangnam St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Kangnam District, Seoul in accordance with procedures approved by the Institutional Review Board of the Catholic University of Korea. The mean serum Se level in healthy subjects was 112.05 +/- 30.42 microg/l. For gender, it was 120.81 +/- 27.37 microg/l for females and 103.29 +/- 31.05 microg/l for males. From the study result, there was a significant difference between the mean Se concentrations of gender groups (p = 0.0035). Also, the study indicated no effect of age on Se levels (p > 0.05) in the healthy individuals.
Asunto(s)
Selenio/sangre , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Factores Sexuales , Adulto JovenRESUMEN
We studied the estrogenic activity and cellular effect of wild yam extract in MCF-7 human breast cancer cells. The extract increased the activity of the progesterone receptor and pS2 genes at the mRNA levels in human breast cancer MCF-7 cells, although the effects were not as prominent as those of 17beta-estradiol (E(2)). Western blot analysis showed that the level of estrogen receptor alpha protein was down-regulated after treatment with E(2) or wild yam extract. Wild yam extract also inhibited proliferation of MCF-7 cells. These data indicate that wild yam extract acts as a weak phytoestrogen and protects against proliferation in human breast carcinoma MCF-7 cells.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Dioscorea , Fitoestrógenos/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Receptores de Progesterona/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Estradiol/farmacología , Estradiol/uso terapéutico , Receptor alfa de Estrógeno/metabolismo , Humanos , Fitoestrógenos/farmacología , Extractos Vegetales/farmacología , Presenilina-2/metabolismo , ARN Mensajero/metabolismoRESUMEN
OBJECTIVES: To evaluate the clinical effect of intraperitoneal hyperthermic chemotherapy (IPHC) in ovarian cancer patients. PATIENTS AND METHODS: We retrospectively reviewed 117 stages Ic-III ovarian cancer patients, who were diagnosed at the Gynecology Department of Kangnam St. Mary's Hospital between January 1994 and January 2000. Of these, 57 patients underwent cytoreductive surgery (conventional treatment) with IPHC and 60 patients (control group) underwent conventional treatment only. IPHC consisted of administering a mixture of 350 mg/m(2) of carboplatin and 5,000,000 IU/m(2) of interferon-alpha, and maintaining the intraperitoneal temperature at 43-44 degrees C during surgery. RESULTS: The overall 5-year survival rate was 58.6%; that of the IPHC group was 63.4% vs. 52.8% in the control group, with significantly higher survival in the IPHC group (P = 0.0078). Considering stage III ovarian cancer patients only (n = 74), the survival rate was 53.8% in the IPHC group (n = 35) and 33.3% in the control group (n = 39) and was significantly higher in the IPHC group (P = 0.0015). For stage III ovarian cancer patients whose tumor was reduced to less than 1 cm during a second procedure (n = 53), the 5-year survival rate was 65.6% in patients who underwent IPHC (n = 26) and 40.7% in the control patients (n = 27) (P = 0.0046). IPHC was an independent prognostic factor that was not affected by surgical staging, tumor size after second surgery, or patient age, according to a multivariate analysis (Hazard ratio = 0.496, P = 0.0176). CONCLUSION: Our study suggests that IPHC is a promising new treatment modality in ovarian cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Hipertermia Inducida , Neoplasias Ováricas/terapia , Adolescente , Adulto , Anciano , Carboplatino/administración & dosificación , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Parenterales , Interferón-alfa/administración & dosificación , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Estudios RetrospectivosRESUMEN
A constituent of green tea, (-)-epigallocatechin-3-gallate (EGCG) has been known to possess antiproliferative properties. In this study, we investigated the anticancer effects of EGCG in human papillomavirus (HPV)-16 associated cervical cancer cell line, CaSki cells. The growth inhibitory mechanism(s) and regulation of gene expression by EGCG were also evaluated. EGCG showed growth inhibitory effects in CaSki cells in a dose-dependent fashion, with an inhibitory dose (ID)(50) of approximately 35 microM. When CaSki cells were further tested for EGCG-induced apoptosis, apoptotic cells were significantly observed after 24 h at 100 microM EGCG. In contrast, an insignificant induction of apoptotic cells was observed at 35 microM EGCG. However, cell cycles at the G1 phase were arrested at 35 microM EGCG, suggesting that cell cycle arrests might precede apoptosis. When CaSki cells were tested for their gene expression using 384 cDNA microarray, an alteration in the gene expression was observed by EGCG treatment. EGCG downregulated the expression of 16 genes over time more than twofold. In contrast, EGCG upregulated the expression of four genes more than twofold, suggesting a possible gene regulatory role of EGCG. This data supports that EGCG can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest as well as regulation of gene expression in vitro. Furthermore, in vivo antitumor effects of EGCG were also observed. Thus, EGCG likely provides an additional option for a new and potential drug approach for cervical cancer patients.