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

Joubert, Annie M.; Maritz, Christine; Joubert, Fourie

doi:10.2220/biomedres.26.87

Cited by 15 publications

(18 citation statements)

References 11 publications

(7 reference statements)

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“…The Bax/Bcl-2 ratio for WHCO3-treated cells was determined as 1.45, normalized against Bcl-2 levels (9). Exposure of human cervical carcinoma cells (HeLa) to PGA 2 and 2-ME revealed a Bax/Bcl-2 ratio of 2.06 and 1.87 respectively, normalized against Bcl-2 levels in these cells, also suggesting that this altered ratio in favor of Bax could lead to the induction of apoptosis in these cells (10).…”

Section: Figmentioning

confidence: 94%

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: Figmentioning

confidence: 94%

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

et al. 2006

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“…The possibility of apoptosis occurred due to intervention with another pathway beside p53 induction as one of Bax activator. Joubert et al, (2005) reported that there was increasing level of Bax and decreasing level of Bcl-2 in Hela due to prostaglandin A 2 and 2-methoxyestradiol treatment. Eventhough Bax expression level was positively regulate by p53, but Bax level remain increasing on p53 mutant cell line like T47D (Butt et al, 2000).…”

Section: Effect Hesperidin and Doxorubicin On Bcl-2 And Bax Expressiomentioning

confidence: 99%

Hesperidin Increase Cytotoxic Activity of Doxorubicin on Hela Cell Line Through Cell Cycle Modulation and Apoptotis Induction

Kusharyanti

Larasati

Susidarti

et al. 2011

Indones J Cancer Chemoprevent

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Combination of chemotherapeutic agent and chemopreventive agent is being a new approach in cancer treatment. This is aimed at enhancing the effectivity and also reducing drug resistance and adverse side effect of the chemotherapeutic agent. Hesperidin, a citrus flavonoid has reported to reduce the proliferation of many cancer cells. The objectives of this study were to investigate cytotoxic activities, cell cycle modulation and apoptosis induction of hesperidin and its combination with doxorubicin on Hela cell lines. MTT [3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide] assay was used to measure the growth inhibitory effect of hesperidin and its combination with doxorubicin on Hela cells. Cell cycle profile was determined by flowcytometry and the data obtained was analyzed by using ModFit LT 3.0 program. Apoptosis assay was done using double staining method using ethidium-bromide and acridine-orange. Hesperidin inhibited cell growth with IC50 48 μM, while the IC50 of doxorubicin was 1000 nM. Combination of 500 nM doxorubicin and 6 μM hesperidin showed strongest inhibitory effect toward Hela cells. Hesperidin of 24 µM accumulated HeLa cells at G1 phase, but its combination with 500 nM Doxorubicin gave G1 and S phase accumulation at 24 h incubation. Both of Hesperidin and Doxorubicin were capable of inducing apoptosis. In accordance of the apoptotic effect, hesperidin, doxorubicin and their combination decreased the expression Bcl-2 and increased the expression of Bax. According to this result, hesperidin has a potency to be developed as co-chemotherapeutic agent for cervical cancer.

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“…5 Current evidence has suggested that 2-ME is the causative agent leading to an increase in Cdc2 kinase activity, the activation of c-Jun NH 2 -terminal kinase signaling, generation of reactive oxygen species and an altered ratio of Bax/ Bcl-2 in favor of Bax, ultimately culminating into apoptosis. [8][9][10][11] Cell division cycle (Cdc) 2 kinase activity is a cell cycle regulatory component essential for commencement of mitosis, whereas Cdc2 inactivation is needed for mitotic exit. Prolonged Cdc2 activity can sustain the cell in mitosis for an indefinite period until particular conditions are met for mitotic exit.…”

Section: Introductionmentioning

confidence: 99%

In vitro effects of 2‐methoxyestradiol on cell numbers, morphology, cell cycle progression, and apoptosis induction in oesophageal carcinoma cells

Thaver

Lottering

Papendorp

et al. 2009

Cell Biochemistry & Function

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The influence of 2-methoxyestradiol (2-ME) was investigated on cell numbers, morphology, cell cycle progression, and apoptosis induction in an oesophageal carcinoma cell line (WHCO3). Dose-dependent studies (1 x 10(-9)M-1 x 10(-6)M) revealed that 2-ME significantly reduced cell numbers to 60% in WHCO3 after 72 h of exposure at a concentration of 1 x 10(-6)M compared to vehicle-treated cells. Morphological studies entailing light-, fluorescent-, as well as transmission electron microscopy (TEM) confirmed 2-ME's antimitotic effects. These results indicated hallmarks of apoptosis including cell shrinkage, hypercondensation of chromatin, cell membrane blebbing, and apoptotic bodies in treated cells. Flow cytometric analyses demonstrated an increase in the G(2)/M-phase after 2-ME exposure; thus preventing cells from proceeding through the cell cycle. beta-tubulin immunofluorescence revealed that 2-ME caused spindle disruption. In addition, increased expression of death receptor 5 protein was observed further supporting the proposed mechanism of apoptosis induction via the extrinsic pathway in 2-ME-exposed oesophageal carcinoma cells.

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

Cited by 15 publications

References 11 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

Hesperidin Increase Cytotoxic Activity of Doxorubicin on Hela Cell Line Through Cell Cycle Modulation and Apoptotis Induction

In vitro effects of 2‐methoxyestradiol on cell numbers, morphology, cell cycle progression, and apoptosis induction in oesophageal carcinoma cells

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