Different Cell Cycle Modulation in SKOV-3 Ovarian Cancer Cell Line by Anti-HIV Drugs
Autor: | Germano Guerra, Angela Lucariello, Antonio De Luca, Angelica Perna, Carmine Sellitto, Iolanda Agliata, Luigi Cobellis, Vincenzo Sangiovanni, Vincenzo Esposito, Maria Aurora Carleo |
---|---|
Přispěvatelé: | Perna, Angelica, Lucariello, Angela, Sellitto, Carmine, Agliata, Iolanda, Carleo, Maria, Sangiovanni, Vincenzo, Esposito, Vincenzo, Guerra, Germano, Cobellis, Luigi, DE LUCA, Antonio |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Cancer Research Efavirenz Anti-HIV Agents Etravirine Adenocarcinoma Antineoplastic effect Article Cell Line 03 medical and health sciences chemistry.chemical_compound Abacavir Ovarian cancer immune system diseases Internal medicine Cell Line Tumor medicine Humans Protease inhibitor (pharmacology) Protease Inhibitors Darunavir Ovarian Neoplasms Tumor Reverse-transcriptase inhibitor business.industry Cell Cycle Antiretroviral drugs Cell cycle virus diseases General Medicine 030104 developmental biology chemistry Cancer cell Cancer research Reverse Transcriptase Inhibitors Female business medicine.drug |
Zdroj: | Oncology Research |
Popis: | Antiretroviral drugs used for the treatment of human immunodeficiency virus (HIV) have proven to be effective even against cancer. Drawing from this background, the aim of our research project was to evaluate the effects of anti-HIV drugs that belong to the nucleoside and nucleotide reverse transcriptase inhibitor [NRTI; abacavir (ABC) and tenofovir (TDF)], nonnucleoside reverse transcriptase inhibitor [NNRTI; efavirenz (EFV) and etravirine (ETR)], and protease inhibitor [PI; darunavir (DRV)] categories on ovarian adenocarcinoma cell line SKOV-3. Using FACS analysis, we observed that treatment with NRTIs and NNRTIs showed a block in the G0/G1phase. In particular, ETR displayed a relevant block in the progression of the G0/G1phase of the cell cycle compared with the other examined drugs, and it also induced differentiation of SKOV-3 cells. In contrast, FACS analysis demonstrated that ABC and the PI inhibitor DRV showed no effect on the proliferation of cancer cells. DAPI (4′,6-diamidino-2-phenylindole) staining demonstrated that cells treated with NNRTIs (EFV and ETR) presented more DNA damage compared with other treatments. Immunoblotting analysis demonstrated that TDF, EFV, and ETR were able to obtain a reduction in the expression of cyclin D1 and Rb hypophosphorylation, and an increase in p21 concentration. Finally, we observed that ETR also induced differentiation, as demonstrated by Western blot, with high levels of E-cadherin expression. Therefore, our study provides additional evidence supporting the in vitro cytotoxic effects of ETR and EFV. Furthermore, it promotes the hypothesis for their potential use as therapeutic agents in ovarian cancer. |
Databáze: | OpenAIRE |
Externí odkaz: |