Fumonisin B1influenced the effects of arachidonic acid, prostaglandins E2 and A2 on cell cycle progression, apoptosis induction, tyrosine- and CDC2-kinase activity in oesophageal cancer cells

Seegers, J.C.; Joubert, Annie M.; Panzer, Annie; Lottering, Mona-Liza; Jordan, Clayton; Joubert, Fourie; Maree, J.L.; Bianchi, Pepita; Kock, Maryna de; Gelderblom, Wentzel C. A.

doi:10.1054/plef.1999.0129

Cited by 17 publications

(9 citation statements)

References 25 publications

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“…Addition of PG E 2 counteracts the mitoinhibitory effect of FB 1 on the EGF mitogenic response in primary hepatocytes, suggesting the disruption of 20:4n-6 metabolism (7). FB 1 also inhibits the effects of 20:4n-6, PG-E 2 , and PG-A 2 on apoptosis in esophageal cancer cells in vitro presumably related to decreased ceramide production (9).…”

Section: Discussionmentioning

confidence: 93%

“…Recent findings indicated that the mitoinhibitory effect of FB 1 was counteracted by prostaglandin (PG) E 2 , suggesting that arachidonic acid (20:4n-6) metabolism is a key determinant affected by FB 1 (7). The modulation of FB 1 on 20:4n-6 and PG-induced effects on cell cycle progression and apoptosis have been reported (8,9). When considering the FA profiles in hepatocytes exposed to FB 1 , it has been suggested that the rate-limiting enzyme in FA metabolism, ∆6-desaturase, is impaired (5).…”

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confidence: 99%

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Lipids and Δ6‐desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B₁

Gelderblom¹,

Moritz²,

Swanevelder³

et al. 2002

Lipids

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Alterations in the membrane structure and function of hepatocyte membranes by fumonisin B1 (FB1) have been proposed to play an important role in the disruption of growth regulatory effects and hence in the cancer-promoting ability of the mycotoxin. Detailed analyses of lipids in liver microsomal fractions of rats exposed to different dietary levels of FB1 over a period of 21 d indicated an increase in PC, PE, PI, and cholesterol (Chol). These changes decreased the PC/PE and increased the total phospholipid/Chol ratios. When considering FA content, the quantities of total FA increased (P < 0.05) in the major phospholipid fractions as a result of the increased phospholipid levels. However, when considering the relative levels (mg/100 mg of the total FA) of specific FA, the monounsaturated FA (16:1 n-7 and 18:1n-9) and 18:2n-6 increased (P < 0.05), whereas the long-chain PUFA decreased (P < 0.05) in the main phospholipid fractions. Enzyme analyses indicated that the activity of the delta6-desaturase was significantly reduced in liver microsomal preparations in a dose-dependent manner. An increase in the 20:3n-6/20:4n-6 ratio also suggested a decrease in the activity of the delta5-desaturase. Disruption of microsomal lipid metabolism at different levels by FB1 could play an important role in the alteration of growth regulatory effects in the liver.

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Section: Discussionmentioning

confidence: 93%

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Lipids and Δ6‐desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B₁

Gelderblom¹,

Moritz²,

Swanevelder³

et al. 2002

Lipids

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“…Premature activation of p34(cdc2) has been implicated as a prerequisite for apoptosis induction in cells arrested in G 2 /M (27). In addition, Seegers et al (2000) demonstrated a decrease in p34(cdc2) activity in PGA 2 -treated WHCO3 oesophageal carcinoma cells (24). In this study confirmation of apoptosis was determined by employing the mitosensor reagent that detects potential changes in the mitochondrial membrane.…”

Section: Figmentioning

confidence: 88%

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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“…Arachidonic acid (C20:4x6) has been associated with the growth regulatory effects of FB 1 in primary hepatocytes and cancer cells [24,76]. It was hypothesized that the increase of C20:4x6 in the PE phospholipids fraction together with the decrease of long-chain PUFA and associated low levels of lipid peroxidation are early events in the neoplastic transformation of hepatic nodules [44].…”

Section: Discussionmentioning

confidence: 99%

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B₁

Burger

Abel

Snijman

et al. 2007

Lipids

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Alteration of lipid constituents of cellular membranes has been proposed as a possible mechanism for cancer promotion by fumonisin B(1 )(FB(1)). To further investigate this hypothesis a dietary dosage which initiates and promotes liver cancer (250 mg FB(1)/kg) was fed to male Fischer rats for 21 days and the lipid composition of plasma, microsomal, mitochondrial and nuclear subcellular fractions determined. The effect of FB(1) on the cholesterol, phosphatidylcholine (PC) and phosphatidylethanolamine (PE), as well as sphingomyelin (SM) and the phospholipids-associated fatty acid (FA) profiles, were unique for each subcellular membrane fraction. PE was significantly increased in the microsomal, mitochondrial and plasma membrane fractions, whereas cholesterol was increased in both the microsomal and nuclear fraction. In addition SM was decreased and increased in the mitochondrial and nuclear fractions, respectively. The decreased PC/PE and polyunsaturated/saturated (P/S) FA ratio in the different membrane fractions suggest a more rigid membrane structure. The decreased levels in polyunsaturated fatty acids in PC together with a pronounced increase in C18:1omega9 and C18:2omega6 were indicative of an impaired delta-6 desaturase. The increased omega6/omega3 ratio and decreased C20:4omega6 PC/PE ratio due to an increase in C20:4omega6 in PE relatively to PC in the different subcellular fractions suggests a shift towards prostanoid synthesis of the E2 series. Changes in the PE and C20:4omega6 parameters in the plasma membrane could alter key growth regulatory and/or other cell receptors in lipid rafts known to be altered by FB(1). An interactive role between C20:4omega6 and ceramide in the mitochondria, is suggested to regulate the balance between proliferation and apoptosis in altered initiated hepatocytes resulting in their selective outgrowth during cancer promotion effected by FB(1).

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Fumonisin B1influenced the effects of arachidonic acid, prostaglandins E2 and A2 on cell cycle progression, apoptosis induction, tyrosine- and CDC2-kinase activity in oesophageal cancer cells

Cited by 17 publications

References 25 publications

Lipids and Δ6‐desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B₁

Lipids and Δ6‐desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B₁

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

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B₁

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Fumonisin B1influenced the effects of arachidonic acid, prostaglandins E2 and A2 on cell cycle progression, apoptosis induction, tyrosine- and CDC2-kinase activity in oesophageal cancer cells

Cited by 17 publications

References 25 publications

Lipids and Δ6‐desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B1

Lipids and Δ6‐desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B1

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

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B1

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Product

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Lipids and Δ6‐desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B₁

Lipids and Δ6‐desaturase activity alterations in rat liver microsomal membranes induced by fumonisin B₁

Altered Lipid Parameters in Hepatic Subcellular Membrane Fractions Induced by Fumonisin B₁