Influence of prostaglandin A2 on Bax, Bcl-2 and PCNA expression in MCF-7 cells.
The effects of 20 microg/mL exogenous prostaglandin A(2) (PGA(2)) were determined on Bax, Bcl-2 and proliferating cell nuclear antigen (PCNA) expression levels in MCF-7 cells. Flow cytometric analysis indicated a pronounced increase in the S phase and a decrease in the G(1) phase, whereas a significant increase in the DNA content preceding the G(0)/G(1) peak was also observed after 48 h of exposure to PGA(2). Confirmation of apoptosis was determined after 12 h, 36 h and 48 h of PGA(2) exposure employing the mitosensor reagent that detects potential changes in the mitochondrial membrane. Twenty-eight percent of PGA(2)-exposed cells were in apoptosis when compared to the 7.1% vehicle-treated cells after 48 h. PGA(2) exposure led to statistically significant increase (1.25-fold) over vehicle-treated controls in Bax expression levels. Decreases in Bcl-2 (0.79-fold), as well as PCNA (0.69-fold) expression levels over vehicle-treated controls were observed. The Bax/Bcl-2 ratio for PGA(2)-exposed cells was 2.7. The present study suggests that an accumulation in the S phase, a decrease in expression levels of PCNA, as well as an altered ratio in favor of Bax, could lead to the induction of apoptosis in these cells.
Joubert
Annie
A
Department of Physiology, University of Pretoria, Pretoria, South Africa. annie.joubert@up.ac.za
Bianchi
Pepita
P
Maritz
Christine
C
Joubert
Fourie
F
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D005434:Flow Cytometry / Q000379:methods; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D011454:Prostaglandins A / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
D018809:Proliferating Cell Nuclear Antigen; D011454:Prostaglandins A; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016650:Fluorescein-5-isothiocyanate; C100008:prostaglandin A2