RESUMO
BACKGROUND: Global trend is moving towards the use of natural phytochemicals to fight against pathogens. Human cervical cancer is directly associated with onco-potent type of Human Papilloma Virus (HPV). There is no known medicine for clearance of HPV type whose persistence is the cause of occurrence and re-occurrence of cervical cancer. The different species of fig fruit and their latex are reported to have HPV associated genital warts clearance capability. METHODS: In the current investigation, the effect of the methanol extract of Ficus benghalensis L. fruits on HPV type18 viral load in HeLa cell line was tested by doing PCR using HPV L1 primers (MY09/My011) and the cytotoxicity was also analysed by MTT assay. The induction of apoptotic activity in terms of DNA fragmentation and hyper-chromic effects of DNA was analysed. RESULTS: The PCR results showed a reduction in the HPV18 DNA and also the treatment exhibited a promising cytotoxicity with IC50 value at 211.86 µg/ml. The DNA samples from treated HeLa cells showed DNA shearing and laddering as a mark of apoptotic DNA fragmentation (Fig. 2) and the UV absorbance value at 260 nm was found to be significantly (p <0.01) higher in the DNA sample treated with fruit extract compared to the untreated DNA sample. CONCLUSION: The Ficus benghalensis L. fruit extract reduced the HPV viral load in HPV18 containing HeLa cells and showed an effective cytotoxicity on HeLa cell line. It also could induce the apoptotic activity in HeLa cell line and this study results suggest that the Ficus benghalensis L. fruits can be used to fight against cervical carcinoma, acting on HPV load.
Assuntos
Apoptose/efeitos dos fármacos , Proteínas do Capsídeo/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Ficus , Papillomavirus Humano 18/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Proteínas do Capsídeo/genética , Sobrevivência Celular/efeitos dos fármacos , Feminino , Frutas , Células HeLa , Papillomavirus Humano 18/genética , Humanos , Neoplasias do Colo do Útero/virologiaRESUMO
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
In this study, we investigated the effects of the aqueous extracts of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum, obtained from three localities (China; and Morelos and Michoacan, Mexico) on cervical cells transformed by human papillomavirus (HeLa and SiHa) and C-33A cancer cells. The cells were plated in DMEM medium supplemented, and were incubated in the presence of different concentrations of G. lucidum for 24 h. Cell proliferation was determined by MTT colorimetric assay and viability by trypan blue assay. Inhibitory dose was determined (IC50) of the three different extracts of G. lucidum in the culture cell lines mentioned above. The apoptosis process was confirmed by nuclear DNA fragmentation and the cell cycle was determined by flow cytometry. The results showed that aqueous extracts G. lucidum obtained from three localities produced inhibition in the proliferation of VPH transformed cells; they also induced apoptosis and cell cycle arrest in HeLa, SiHa, and C-33A cancer cells. Therefore, it was found that aqueous extracts G. lucidum obtained from three different locations produced inhibitory effect on cancer cells and may have a potential therapeutic use for the prevention and treatment of this disease.