title: Effects of HIV protease, nucleoside/non-nucleoside reverse transcriptase inhibitors on Bax, Bcl-2 and apoptosis in two cervical cell lines.
abstract: Protease inhibitors (PIs) and reverse transcriptase drugs are important components of highly active antiretroviral therapy (HAART) for treating human acquired immunodeficiency syndrome (AIDS). Long-term clinical therapeutic efficacy and treatment compliance of these agents have been limited by undesirable adverse effects and their oncogenicity has been queried. This study investigated the effects of selected antiretroviral agents on the expression of key apoptotic regulatory genes; Bax and Bcl-2 in two cervical cell lines HCS-2 and NCE16IIA by real-time qPCR gene expression and immunocytochemistry. The anti-apoptotic effects of the PI-LPV/r were investigated by cell death detection ELISA and acridine orange staining. All the antiretroviral drugs and combinations tested had no effects on Bax and Bcl-2 gene expression and protein localisation in both cell lines. The protease inhibitors-LPV/r exhibited significant (P<0.05) inhibition of camptothecin-induced apoptosis in the cervical cancer HCS-2 cell line but not in the normal immortalised NCE16IIA cell line. This anti-apoptotic property of HIV protease inhibitors, although shown so far not to involve protein and RNA synthesis might promote the development of cancer.
authors.affiliation: School of Anatomical Sciences, Wits Medical School, University of the Witwatersrand, 7, York Road, Parktown, 2193 Johannesburg, South Africa. Electronic address: gbenga.adefolaju@wits.ac.za.
authors.forename: Gbenga Anthony
authors.initials: GA
authors.lastname: Adefolaju
authors.affiliation: Division of Human Genetics, Department of Medical Sciences, University of Limpopo, Private Bag x1106n, Sovenga 0727, South Africa.
authors.forename: Kathrine Elizabeth
authors.initials: KE
authors.lastname: Theron
authors.affiliation: School of Anatomical Sciences, Wits Medical School, University of the Witwatersrand, 7, York Road, Parktown, 2193 Johannesburg, South Africa.
authors.forename: Margot Jill
authors.initials: MJ
authors.lastname: Hosie
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D009705:Nucleosides / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000737:chemistry; D002583:Uterine Cervical Neoplasms / Q000139:chemically induced; D051028:bcl-2-Associated X Protein / Q000235:genetics*
chemical_list: C494826:BAX protein, human; D017320:HIV Protease Inhibitors; D009705:Nucleosides; D019253:Proto-Oncogene Proteins c-bcl-2; D018894:Reverse Transcriptase Inhibitors; D051028:bcl-2-Associated X Protein
keywords: Antiretroviral drugs; Apoptosis; Bax/Bcl-2