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Role of Bax in resveratrol-induced apoptosis of colorectal carcinoma cells.

Mahyar-Roemer M, Köhler H, Roemer K - BMC Cancer (2002)

Bottom Line: In the absence of Bax, membrane potential collapse was delayed, and apoptosis was reduced but not absent.Resveratrol at physiological doses can induce a Bax-mediated and a Bax-independent mitochondrial apoptosis.Both can limit the ability of the cells to form colonies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Virology, Institute of Medical Microbiology, University of Saarland Medical School, D-66421 Homburg/Saar, Germany. inmmah@uniklinik-saarland.de

ABSTRACT

Background: The natural plant polyphenol resveratrol present in some foods including grapes, wine, and peanuts, has been implicated in the inhibition, delay, and reversion of cellular events associated with heart diseases and tumorigenesis. Recent work has suggested that the cancer chemoprotective effect of the compound is primarily linked to its ability to induce cell division cycle arrest and apoptosis, the latter possibly through the activation of pro-apoptotic proteins such as Bax.

Methods: The expression, subcellular localization, and importance of Bax for resveratrol-provoked apoptosis were assessed in human HCT116 colon carcinoma cells and derivatives with both bax alleles inactivated.

Results: Low to moderate concentrations of resveratrol induced co-localization of cellular Bax protein with mitochondria, collapse of the mitochondrial membrane potential, activation of caspases 3 and 9, and finally, apoptosis. In the absence of Bax, membrane potential collapse was delayed, and apoptosis was reduced but not absent. Resveratrol inhibited the formation of colonies by both HCT116 and HCT116 bax -/- cells.

Conclusion: Resveratrol at physiological doses can induce a Bax-mediated and a Bax-independent mitochondrial apoptosis. Both can limit the ability of the cells to form colonies.

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Effect of resveratrol on the survival of the parental HCT116 cells and the bax -/- derivatives in culture. Panel A: Treatment of exponentially growing cultures with different doses of resveratrol for 48 h and quantitation of the numbers of cells with a sub-2n-DNA content by flow-cytometry revealed a dose-dependent increase of apoptosis in both cell lines and a much stronger apoptotic response in the cells expressing Bax, especially at low drug doses. Panel B: Time course of apoptosis in exponentially growing cultures either mock-treated or treated with 100 μM resveratrol, documenting the time-dependence of cell death induction. Note the reduced basal level of apoptosis in the bax -/- cultures. Error bars denote standard deviations of the means of four experiments.
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Figure 4: Effect of resveratrol on the survival of the parental HCT116 cells and the bax -/- derivatives in culture. Panel A: Treatment of exponentially growing cultures with different doses of resveratrol for 48 h and quantitation of the numbers of cells with a sub-2n-DNA content by flow-cytometry revealed a dose-dependent increase of apoptosis in both cell lines and a much stronger apoptotic response in the cells expressing Bax, especially at low drug doses. Panel B: Time course of apoptosis in exponentially growing cultures either mock-treated or treated with 100 μM resveratrol, documenting the time-dependence of cell death induction. Note the reduced basal level of apoptosis in the bax -/- cultures. Error bars denote standard deviations of the means of four experiments.

Mentions: We next asked how the survival of HCT116 and HCT116 bax -/- cultures is affected by resveratrol. When cells were incubated for 48 h in the presence of increasing concentrations of resveratrol and subsequently FACS-scanned for cell size and DNA content, a dose-dependent induction of apoptosis was observed in both cultures (Figure 4A). In HCT116 cultures, the rate of apoptosis increased to approximately 25 % at 20 μM resveratrol and plateaued thereafter. Although the bax-deficient cultures showed a similar dose-dependence of apoptosis, the rate of cell death was significantly lower. A time course over 96 h confirmed that resveratrol at 100 μM can provoke apoptosis in both cell lines, but much less efficiently in the bax -/- cells (Figure 4B), documenting that resveratrol-induced apoptosis in HCT116 cells is in part, but not entirely, dependent on Bax.


Role of Bax in resveratrol-induced apoptosis of colorectal carcinoma cells.

Mahyar-Roemer M, Köhler H, Roemer K - BMC Cancer (2002)

Effect of resveratrol on the survival of the parental HCT116 cells and the bax -/- derivatives in culture. Panel A: Treatment of exponentially growing cultures with different doses of resveratrol for 48 h and quantitation of the numbers of cells with a sub-2n-DNA content by flow-cytometry revealed a dose-dependent increase of apoptosis in both cell lines and a much stronger apoptotic response in the cells expressing Bax, especially at low drug doses. Panel B: Time course of apoptosis in exponentially growing cultures either mock-treated or treated with 100 μM resveratrol, documenting the time-dependence of cell death induction. Note the reduced basal level of apoptosis in the bax -/- cultures. Error bars denote standard deviations of the means of four experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC130964&req=5

Figure 4: Effect of resveratrol on the survival of the parental HCT116 cells and the bax -/- derivatives in culture. Panel A: Treatment of exponentially growing cultures with different doses of resveratrol for 48 h and quantitation of the numbers of cells with a sub-2n-DNA content by flow-cytometry revealed a dose-dependent increase of apoptosis in both cell lines and a much stronger apoptotic response in the cells expressing Bax, especially at low drug doses. Panel B: Time course of apoptosis in exponentially growing cultures either mock-treated or treated with 100 μM resveratrol, documenting the time-dependence of cell death induction. Note the reduced basal level of apoptosis in the bax -/- cultures. Error bars denote standard deviations of the means of four experiments.
Mentions: We next asked how the survival of HCT116 and HCT116 bax -/- cultures is affected by resveratrol. When cells were incubated for 48 h in the presence of increasing concentrations of resveratrol and subsequently FACS-scanned for cell size and DNA content, a dose-dependent induction of apoptosis was observed in both cultures (Figure 4A). In HCT116 cultures, the rate of apoptosis increased to approximately 25 % at 20 μM resveratrol and plateaued thereafter. Although the bax-deficient cultures showed a similar dose-dependence of apoptosis, the rate of cell death was significantly lower. A time course over 96 h confirmed that resveratrol at 100 μM can provoke apoptosis in both cell lines, but much less efficiently in the bax -/- cells (Figure 4B), documenting that resveratrol-induced apoptosis in HCT116 cells is in part, but not entirely, dependent on Bax.

Bottom Line: In the absence of Bax, membrane potential collapse was delayed, and apoptosis was reduced but not absent.Resveratrol at physiological doses can induce a Bax-mediated and a Bax-independent mitochondrial apoptosis.Both can limit the ability of the cells to form colonies.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Virology, Institute of Medical Microbiology, University of Saarland Medical School, D-66421 Homburg/Saar, Germany. inmmah@uniklinik-saarland.de

ABSTRACT

Background: The natural plant polyphenol resveratrol present in some foods including grapes, wine, and peanuts, has been implicated in the inhibition, delay, and reversion of cellular events associated with heart diseases and tumorigenesis. Recent work has suggested that the cancer chemoprotective effect of the compound is primarily linked to its ability to induce cell division cycle arrest and apoptosis, the latter possibly through the activation of pro-apoptotic proteins such as Bax.

Methods: The expression, subcellular localization, and importance of Bax for resveratrol-provoked apoptosis were assessed in human HCT116 colon carcinoma cells and derivatives with both bax alleles inactivated.

Results: Low to moderate concentrations of resveratrol induced co-localization of cellular Bax protein with mitochondria, collapse of the mitochondrial membrane potential, activation of caspases 3 and 9, and finally, apoptosis. In the absence of Bax, membrane potential collapse was delayed, and apoptosis was reduced but not absent. Resveratrol inhibited the formation of colonies by both HCT116 and HCT116 bax -/- cells.

Conclusion: Resveratrol at physiological doses can induce a Bax-mediated and a Bax-independent mitochondrial apoptosis. Both can limit the ability of the cells to form colonies.

Show MeSH
Related in: MedlinePlus