RESUMO
Human telomerase reverse transcriptase (hTERT) is an enzyme that is critically involved in elongating and maintaining telomeres length to control cell life span and replicative potential. Telomerase activity is continuously expressed in human germ-line cells and most cancer cells, whereas it is suppressed in most somatic cells. In normal cells, by reducing telomerase activity and progressively shortening the telomeres, the cells progress to the senescence or apoptosis process. However, in cancer cells, telomere lengths remain constant due to telomerase's reactivation, and cells continue to proliferate and inhibit apoptosis, and ultimately lead to cancer development and human death due to metastasis. Studies demonstrated that several DNA and RNA oncoviruses could interact with telomerase by integrating their genome sequence within the host cell telomeres specifically. Through the activation of the hTERT promoter and lengthening the telomere, these cells contributes to cancer development. Since oncoviruses can activate telomerase and increase hTERT expression, there are several therapeutic strategies based on targeting the telomerase of cancer cells like telomerase-targeted peptide vaccines, hTERT-targeting dendritic cells (DCs), hTERT-targeting gene therapy, and hTERT-targeting CRISPR/Cas9 system that can overcome tumor-mediated toleration mechanisms and specifically apoptosis in cancer cells. This study reviews available data on the molecular structure of telomerase and the role of oncoviruses and telomerase interaction in cancer development and telomerase-dependent therapeutic approaches to conquest the cancer cells.
Assuntos
Neoplasias/genética , Proteínas Oncogênicas Virais/metabolismo , Retroviridae/patogenicidade , Telomerase/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/genética , Senescência Celular/genética , Modelos Animais de Doenças , Terapia Genética/métodos , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Camundongos , Neoplasias/terapia , Neoplasias/virologia , Proteínas Oncogênicas Virais/genética , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia , Regiões Promotoras Genéticas , Retroviridae/genética , Telomerase/antagonistas & inibidores , Telômero/metabolismo , Homeostase do TelômeroRESUMO
Background: Colorectal cancer (CRC) is widespread across the world. While conventional anticancer treatments can help the affected patients, cells of vital organs such as the kidney, lungs, bladder and nervous system may suffer from side effects of chemotherapeutic drugs, so that it is necessary to search for alternatives. From ancient times, attention has focused on medicinal plants and natural products. In the current work, Camellia sinensis, whose leaves are used to produce green tea was evaluated for anticancer effects in cell culture. Materials and Methods: A hydroalcoholic extract of Camellia sinensis young leaves was prepared by percolation and compared with Cisplatin as a known anticancer drug for effects on two cell lines: Caco-2, colon carcinoma cells, and mouse normal fibroblasts (L929). Cytotoxicity of 50, 100, 200, 400 and 800 µg/ml of Camellia sinensis extract was evaluated by MTT assay and aquaporin 5 (AQP5), detected as a biomarker for surviving cells using immunofluorescence microscopy. Results: MTT assays with hydroalcoholic extract of Camellia sinensis showed considerable inhibition of growth of Caco-2 cells, significant at 800 µg/ml (P<0.05), with little effect on L929 cells. Levels of aquaporin 5 protein decreased in Caco-2 cell culture following green tea extract treatment. Conclusion: According to the results of the current study, Camellia sinensis is a medicinal plant with potent anticancer influence which might be specific.