Open Access

ARTICLE

Different Cell Cycle Modulation in SKOV-3 Ovarian Cancer Cell Line by Anti-HIV Drugs

Angelica Perna^*†, Angela Lucariello^*†, Carmine Sellitto^*, Iolanda Agliata^†, Maria Aurora Carleo^‡, Vincenzo Sangiovanni^‡, Vincenzo Esposito^§, Germano Guerra^†, Luigi Cobellis^¶, Antonio De Luca^*

* Department of Mental and Physical Health and Preventive Medicine, Section of Human Anatomy, Università degli Studi della Campania “L. Vanvitelli”, Naples, Italy
† Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy
‡ III UOC of Infectious Diseases P.O. Cotugno, AO Ospedale dei Colli, Naples, Italy
§ V UOC of Infectious Diseases P.O. Cotugno, AO Ospedale dei Colli, Naples, Italy
¶ Department of Gynecology, Obstetric and Reproductive Science, Università degli Studi della Campania “L. Vanvitelli”, Naples, Italy

Oncology Research 2017, 25(9), 1617-1624. https://doi.org/10.3727/096504017X14905635363102

Abstract

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/G₁ phase. In particular, ETR displayed a relevant block in the progression of the G₀/G₁ 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.

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