RBBP6: a potential biomarker of apoptosis induction in human cervical cancer cell lines
| Autor: | Lesetja Raymond Motadi, Pontsho Moela |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell cycle checkpoint Tumor suppressor gene Biology OncoTargets and Therapy Flow cytometry 03 medical and health sciences chemistry.chemical_compound GABA xCELLigence medicine Pharmacology (medical) Propidium iodide Original Research medicine.diagnostic_test Cell growth camptothecin apoptosis Cancer medicine.disease Molecular biology 030104 developmental biology Oncology chemistry Apoptosis silencing Camptothecin medicine.drug overexpression |
| Zdroj: | OncoTargets and therapy |
| ISSN: | 1178-6930 |
| Popis: | Pontsho Moela, Lesetja Raymond Motadi Department of Biochemistry, North-West University, Potchefstroom, South Africa Abstract: Overexpression of RBBP6 in cancers of the colon, lung, and esophagus makes it a potential target in anticancer therapy. This is especially important because RBBP6 associates with the tumor suppressor gene p53, the inactivation of which has been linked to over 50% of all cancer types. However, the expression of RBBP6 in cancer and its interaction with p53 are yet to be understood in order to determine whether or not RBBP6 is cancer promoting and therefore a potential biomarker. In this study, we manipulated RBBP6 expression levels followed by treatment with either camptothecin or γ-aminobutyric acid in cervical cancer cells to induce apoptosis or cell cycle arrest. We began by staining human cervical cancer tissue sections with anti-RBBP6 monoclonal antibody to evaluate the extent of expression of RBBP6 in patients’ specimens. We followed on with silencing the overexpression of RBBP6 and treatment with anticancer agents to evaluate how the specimens respond to combinational therapy. Apoptosis induction was evaluated through confocal microscope, and flow cytometry using annexin V staining, and also by checking the mitochondrial and caspase-3/7 activity. Cell cycle arrest was evaluated using flow cytometry through staining with propidium iodide. RBBP6 was highly expressed in cervical cancer tissue sections that were in stage II or III of development. Silencing RBBP6 followed by treatment with γ-aminobutyric acid and camptothecin seems to sensitize cells to apoptosis induction rather than cell cycle arrest. Overexpression of RBBP6 seems to promote S-phase in cell cycle and cell proliferation. These results predict a proliferative role of RBBP6 in cancer progression rather than as a cancer-causing gene. Furthermore, sensitization of cells to camptothecin-induced apoptosis by RBBP6 targeting suggests a promising tool for halting cervical cancer progression. Keywords: xCELLigence, camptothecin, GABA, apoptosis, silencing, overexpression |
| Databáze: | OpenAIRE |
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