scholarly journals In-vitro effects of protease inhibitors on BAX, BCL- 2 and apoptosis in two human breast cell lines

2015 ◽  
Vol Volume 111 (Number 11/12) ◽  
Author(s):  
Gbenga A. Adefolaju ◽  
Kathrine E. Theron ◽  
Margot J. Hosie ◽  
◽  
◽  
...  

Abstract Currently, the treatment of choice of HIV/AIDS in South Africa is the multidrug combination regimen known as HAART (highly active antiretroviral treatment). HAART, which commonly consists of nucleoside or non-nucleoside reverse transcriptase inhibitors and protease inhibitors, has radically decreased mortality and morbidity rates among people living with HIV/AIDS. The emphasis of the original development of the antiretroviral drugs was on clinical effectiveness (reducing mortality). Presently, emphasis has shifted from the initial short- term considerations to the long-term undesirable or harmful effects induced by this treatment regimen. Whether antiretroviral compounds are oncogenic is widely speculated, which led to this investigation into the effects of protease inhibitors on the expression of key apoptotic regulatory genes, BAX and BCL-2, in two human breast cell lines, MCF-7 and MCF-10A by real-time qPCR gene expression and immunofluorescence. The anti-apoptotic effects of the protease inhibitors – LPV/r were also investigated by cell death detection ELISA and acridine orange staining. This study also evaluated the cytotoxicity of the antiretroviral drugs in normal and cancer cell lines of the breast (at clinically relevant concentrations of the drugs and at different time points, 24–96 h), employing the neutral red uptake assay. The drugs and combinations tested did not alter BAX and BCL-2 gene expression and protein expression and localisation in both cell lines. In addition, the protease inhibitors–LPV/r did not inhibit camptothecin-induced apoptosis in both cell lines. We have shown that the protease inhibitors demonstrated varying degrees of cytotoxicity in the breast cells. The resulting DNA damage associated with cytotoxicity is strongly implicated in the processes of tumour initiation.

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin Morgan ◽  
Colette Meyer ◽  
Nicola Miller ◽  
Andrew H Sims ◽  
Ilgin Cagnan ◽  
...  

1995 ◽  
Vol 35 (2) ◽  
pp. 211-220 ◽  
Author(s):  
Lisa D. Laury-Kleintop ◽  
Elizabeth C. Coronel ◽  
Marianne K. Lange ◽  
Thomas Tachovsky ◽  
Santo Longo ◽  
...  

2015 ◽  
Vol 67 (8) ◽  
pp. 1344-1356 ◽  
Author(s):  
Hanna Szaefer ◽  
Violetta Krajka-Kuźniak ◽  
Barbara Licznerska ◽  
Agnieszka Bartoszek ◽  
Wanda Baer-Dubowska

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Carmen Ortiz ◽  
Luisa Morales ◽  
Miguel Sastre ◽  
William E. Haskins ◽  
Jaime Matta

Sandalwood essential oil (SEO) is extracted fromSantalumtrees. Althoughα-santalol, a main constituent of SEO, has been studied as a chemopreventive agent, the genotoxic activity of the whole oil in human breast cell lines is still unknown. The main objective of this study was to assess the cytotoxic and genotoxic effects of SEO in breast adenocarcinoma (MCF-7) and nontumorigenic breast epithelial (MCF-10A) cells. Proteins associated with SEO genotoxicity were identified using a proteomics approach. Commercially available, high-purity, GC/MS characterized SEO was used to perform the experiments. The main constituents reported in the oil were (Z)-α-santalol (25.34%), (Z)-nuciferol (18.34%), (E)-β-santalol (10.97%), and (E)-nuciferol (10.46%). Upon exposure to SEO (2–8 μg/mL) for 24 hours, cell proliferation was determined by the MTT assay. Alkaline and neutral comet assays were used to assess genotoxicity. SEO exposure induced single- and double-strand breaks selectively in the DNA of MCF-7 cells. Quantitative LC/MS-based proteomics allowed identification of candidate proteins involved in this response: Ku70 (p=1.37E-2), Ku80 (p=5.8E-3), EPHX1 (p=3.3E-3), and 14-3-3ζ(p=4.0E-4). These results provide the first evidence that SEO is genotoxic and capable of inducing DNA single- and double-strand breaks in MCF-7 cells.


2005 ◽  
Vol 58 (1) ◽  
pp. 50-61 ◽  
Author(s):  
Stella Maris Vázquez ◽  
Alejandro Gustavo Mladovan ◽  
Cecilia Pérez ◽  
Ariana Bruzzone ◽  
Alberto Baldi ◽  
...  

PLoS ONE ◽  
2010 ◽  
Vol 5 (3) ◽  
pp. e9738 ◽  
Author(s):  
William C. Hines ◽  
Alexey V. Bazarov ◽  
Rituparna Mukhopadhyay ◽  
Paul Yaswen

2012 ◽  
Vol 14 (2) ◽  
pp. 329-344 ◽  
Author(s):  
Bo Yuan ◽  
Linglan Wang ◽  
Yi Jin ◽  
Huijuan Zhen ◽  
Pingwei Xu ◽  
...  

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