The effects of prostaglandin A2 on cell growth, cell cycle status and apoptosis induction in HeLa and MCF-7 cells

Joubert, Annie M.; Panzer, Annie; Bianchi, Pepita; Lottering, Mona-Liza

doi:10.1016/s0304-3835(02)00625-0

Cited by 17 publications

(15 citation statements)

References 25 publications

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“…We have shown that 20 μg/mL PGA 2 significantly decreased cell numbers of HeLa (cervical carcinoma) and MCF-7 cells, with the latter cell line being more susceptible to PGA 2 's anti-mitogenic effects (11). These anti-mitogenic effects were confirmed by morphological studies, mitotic indices and flow cytometry, as well as propidium iodide and Hoechst 33342 cell staining conducted after 48 h of exposure to PGA 2 .…”

Section: Discussionmentioning

confidence: 61%

“…These anti-mitogenic effects were confirmed by morphological studies, mitotic indices and flow cytometry, as well as propidium iodide and Hoechst 33342 cell staining conducted after 48 h of exposure to PGA 2 . Results suggested that the decrease in cell numbers initially observed was probably not due to inhibition of proliferation, but could be ascribed to an induction of apoptosis resulting in cell death (11). The aim of this study was therefore to confirm the anti-mitogenic effects of PGA 2 and to investigate the influence of PGA 2 on Bax, Bcl-2 and PCNA expression levels in MCF-7 cells in order to suggest a was monitored at 450 nm with a SLT 340 ATC scanner (SLT Labinstruments, Austria).…”

Section: Discussionmentioning

confidence: 93%

“…PGA 2 inhibited proliferation of tumor cells depending on dose, duration of exposure and cell type (12). In addition, we have demonstrated that the breast adenocarcinoma cells, MCF-7, were more susceptible to the anti-mitogenic effects of PGA 2 when compared to human epithelial cervix carcinoma (HeLa) cells (11). Furthermore, degree of differentiation of oesophageal carcinoma cells was also shown to influence tumor cell susceptibility to the anti-mitogenic effects of PGA 2 .…”

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confidence: 78%

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Influence of prostaglandin A2 on Bax, Bcl-2 and PCNA expression in MCF-7 cells

et al. 2006

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The effects of 20 μg/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.Research has shown that prostaglandin A 2 (PGA 2 ), a cyclopentenone and endogenous metabolite derived from arachidonic acid, exhibits potent anti-proliferative activity in vivo (5,14,20,22) and in vitro (1, 17-19, 21, 23). Concentration-dependent studies from previous research (12) revealed that 20 μg/mL results in optimal growth inhibition in vitro. This was confirmed in our laboratory where IC 50 = 20 μg/ mL was determined (results not shown). PGA 2 inhibited proliferation of tumor cells depending on dose, duration of exposure and cell type (12). In addition, we have demonstrated that the breast adenocarcinoma cells, MCF-7, were more susceptible to the anti-mitogenic effects of PGA 2 when compared to human epithelial cervix carcinoma (HeLa) cells (11). Furthermore, degree of differentiation of oesophageal carcinoma cells was also shown to influence tumor cell susceptibility to the anti-mitogenic effects of PGA 2 . More differentiated and normal cells appeared to be less affected, while more pronounced effects were observed in less differentiated cell lines (12).Since PGA 2 targets active proliferating cells and plays an active role in the induction of apoptosis, especially in cells that present with carcinogenic properties (12,25), the aim of this study was to confirm the anti-mitogenic effects of PGA 2 and to investigate the influence of PGA 2 on Bax, Bcl-2 and PCNA expression in MCF-7 cells in order to suggest a possible mechanism for induction of apoptosis.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 78%

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Influence of prostaglandin A2 on Bax, Bcl-2 and PCNA expression in MCF-7 cells

et al. 2006

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“…Our previous research has already revealed that PGA 2 and 2-ME caused signifi cant decreases in cell growth, overexpression of extracellular signal regulated protein kinase (ERK1/2) and subsequent induction of apoptosis in HeLa cells (3,4,9). These results suggested that the increased ratio of proapoptotic Bax to anti-apoptotic Bcl-2 appear to be associated with both the PGA 2 -and 2-ME-induced apoptosis observed in HeLa cells.…”

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confidence: 88%

Influence of prostaglandin A2 and 2-methoxyestradiol on Bax and Bcl-2 expression levels in cervical carcinoma cells

2005

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“…Cell numbers were determined spectrophotometrically with crystal violet as a DNA stain (Joubert et al, 2003).…”

Section: Determination Of Cell Numbersmentioning

confidence: 99%

Influence of Sutherlandia frutescens extracts on cell numbers, morphology and gene expression in MCF-7 cells

Stander

Marais

Steynberg

et al. 2007

Journal of Ethnopharmacology

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Sutherlandia frutescens is a well-known South African herbal remedy traditionally used for stomach problems, internal cancers, diabetes, various inflammatory conditions and recently to improve the overall health in cancer and HIV/AIDS patients. The influence of crude Sutherlandia frutescens extracts (prepared with 70% ethanol) was investigated on cell numbers, morphology, and gene expression profiles in a MCF-7 human breast adenocarcinoma cell line. Time-dependent (24, 34, 48 and 72 h) and dose-dependent (0.5-2.5 mg/ml) studies were conducted utilizing spectrophotometrical analysis with crystal violet as DNA stain. A statistically significant decrease to 50% of malignant cell numbers was observed after 24 h of exposure to 1.5 mg/ml Sutherlandia frutescens extract when compared to vehicle-treated controls. Morphological characteristics of apoptosis including cytoplasmic shrinking, membrane blebbing and apoptotic bodies were observed after 24 h of exposure. A preliminary global gene expression profile was o op pe en nU UP P ( (J Ju un ne e 2 20 00 07 7) ) obtained by means of microarray analysis and revealed valuable information about the molecular mechanisms and signal transduction associated with 70% ethanolic Sutherlandia frutescens extracts.

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The effects of prostaglandin A2 on cell growth, cell cycle status and apoptosis induction in HeLa and MCF-7 cells

Cited by 17 publications

References 25 publications

Influence of prostaglandin A2 on Bax, Bcl-2 and PCNA expression in MCF-7 cells

Influence of prostaglandin A2 on Bax, Bcl-2 and PCNA expression in MCF-7 cells

Influence of prostaglandin A2 and 2-methoxyestradiol on Bax and Bcl-2 expression levels in cervical carcinoma cells

Influence of Sutherlandia frutescens extracts on cell numbers, morphology and gene expression in MCF-7 cells

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