TY  - EJOU
AU  - Perna, Angelica 
AU  - Lucariello, Angela 
AU  - Sellitto, Carmine 
AU  - Agliata, Iolanda 
AU  - Carleo, Maria Aurora 
AU  - Sangiovanni, Vincenzo 
AU  - Esposito, Vincenzo 
AU  - Guerra, Germano 
AU  - Cobellis, Luigi 
AU  - Luca, Antonio De 

TI  - Different Cell Cycle Modulation in SKOV-3 Ovarian Cancer Cell Line  by Anti-HIV Drugs
T2  - Oncology Research

PY  - 2017
VL  - 25
IS  - 9
SN  - 1555-3906

AB  - 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 G<sub>0</sub>/G<sub>1</sub> phase. In particular, ETR displayed a relevant block in the progression of the G<sub>0</sub>/G<sub>1</sub> phase 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.
KW  - Cell cycle; Ovarian cancer; Antiretroviral drugs; Antineoplastic effect

DO  - 10.3727/096504017X14905635363102