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Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells

View Article: PubMed Central - PubMed

ABSTRACT

Accumulating evidence suggests that natural bioactive compounds, alone or in combination with traditional chemotherapeutic agents, could be used as potential therapies to fight cancer. In this study, we employed four natural bioactive compounds (curcumin, resveratrol, melatonin, and silibinin) and studied their role in redox control and ability to promote apoptosis in androgen sensitive and insensitive prostate cancer cells. Here is shown that curcumin and resveratrol promote ROS production and induce apoptosis in LNCaP and PC-3. An increase in reactive species is a trigger event in curcumin-induced apoptosis and a consequence of resveratrol effects on other pathways within these cells. Moreover, here we demonstrated that these four compounds affect differently one of the main intracellular redox regulator, the thioredoxin system. Exposure to curcumin and resveratrol promoted TRX1 oxidation and altered its subcellular location. Furthermore, resveratrol diminished TRX1 levels in PC-3 cells and increased the expression of its inhibitor TXNIP. Conversly, melatonin and silibinin only worked as cytostatic agents, reducing ROS levels and showing preventive effects against TRX oxidation. All together, this work explores the effect of compounds currently tested as chemo-preventive agents in prostate cancer therapy, on the TRX1 redox state and function. Our work shows the importance that the TRX system might have within the differences found in their mechanisms of action. These bioactive compounds trigger different responses and affect ROS production and redox systems in prostate cancer cells, suggesting the key role that redox-related pathways might play in processes like differentiation or survival in prostate cancer.

No MeSH data available.


Related in: MedlinePlus

Influence of NAC on curcumin and resveratrol-induced toxicity. LNCaP (A) and PC-3 cells (B) were incubated with curcumin (25, 50 and 100 μM) alone or prior 3 h incubation with 20 mM NAC. Cell viability was measured by MTT assay after 24 h treatment. PC-3 cells were treated with curcumin alone (C) or after prior incubation with NAC (D) for 36 h. Apoptosis was measured by flow cytometry after staining with Annexin V/PI. LNCaP (E) and PC-3 cells (F) were treated with resveratrol (25, 50 and 100 µM). Cell viability was measured with MTT assay after 24 h. *p<0.05; **p<0.01; ***p<0.001 versus CON.
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f0020: Influence of NAC on curcumin and resveratrol-induced toxicity. LNCaP (A) and PC-3 cells (B) were incubated with curcumin (25, 50 and 100 μM) alone or prior 3 h incubation with 20 mM NAC. Cell viability was measured by MTT assay after 24 h treatment. PC-3 cells were treated with curcumin alone (C) or after prior incubation with NAC (D) for 36 h. Apoptosis was measured by flow cytometry after staining with Annexin V/PI. LNCaP (E) and PC-3 cells (F) were treated with resveratrol (25, 50 and 100 µM). Cell viability was measured with MTT assay after 24 h. *p<0.05; **p<0.01; ***p<0.001 versus CON.

Mentions: Since an early increase in ROS levels combined with a decrease in catalase likely explains the mechanism of action of curcumin in LNCaP and PC-3 cells, we tried to evaluate whether curcumin effect on cell viability could be prevented by incubation with N-acetyl-cysteine (NAC), a precursor of glutathione (GSH). LNCaP (Fig. 4A) and PC-3 cells (Fig. 4B) were pre-treated with 20 mM NAC for 3 h and then exposed to increasing concentrations of curcumin (25, 50, and 100 µM). The effect of curcumin on cell viability was greatly inhibited by pre-incubation with NAC in both cell lines (Fig. 4A, B). In addition, pre-incubation with NAC decreased nearly 90% the number of apoptotic cells in the group treated with 100 µM curcumin (Fig. 4C), supporting that the toxicity mediated by this compound might involve changes in redox state in prostate cancer cells.


Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells
Influence of NAC on curcumin and resveratrol-induced toxicity. LNCaP (A) and PC-3 cells (B) were incubated with curcumin (25, 50 and 100 μM) alone or prior 3 h incubation with 20 mM NAC. Cell viability was measured by MTT assay after 24 h treatment. PC-3 cells were treated with curcumin alone (C) or after prior incubation with NAC (D) for 36 h. Apoptosis was measured by flow cytometry after staining with Annexin V/PI. LNCaP (E) and PC-3 cells (F) were treated with resveratrol (25, 50 and 100 µM). Cell viability was measured with MTT assay after 24 h. *p<0.05; **p<0.01; ***p<0.001 versus CON.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5385622&req=5

f0020: Influence of NAC on curcumin and resveratrol-induced toxicity. LNCaP (A) and PC-3 cells (B) were incubated with curcumin (25, 50 and 100 μM) alone or prior 3 h incubation with 20 mM NAC. Cell viability was measured by MTT assay after 24 h treatment. PC-3 cells were treated with curcumin alone (C) or after prior incubation with NAC (D) for 36 h. Apoptosis was measured by flow cytometry after staining with Annexin V/PI. LNCaP (E) and PC-3 cells (F) were treated with resveratrol (25, 50 and 100 µM). Cell viability was measured with MTT assay after 24 h. *p<0.05; **p<0.01; ***p<0.001 versus CON.
Mentions: Since an early increase in ROS levels combined with a decrease in catalase likely explains the mechanism of action of curcumin in LNCaP and PC-3 cells, we tried to evaluate whether curcumin effect on cell viability could be prevented by incubation with N-acetyl-cysteine (NAC), a precursor of glutathione (GSH). LNCaP (Fig. 4A) and PC-3 cells (Fig. 4B) were pre-treated with 20 mM NAC for 3 h and then exposed to increasing concentrations of curcumin (25, 50, and 100 µM). The effect of curcumin on cell viability was greatly inhibited by pre-incubation with NAC in both cell lines (Fig. 4A, B). In addition, pre-incubation with NAC decreased nearly 90% the number of apoptotic cells in the group treated with 100 µM curcumin (Fig. 4C), supporting that the toxicity mediated by this compound might involve changes in redox state in prostate cancer cells.

View Article: PubMed Central - PubMed

ABSTRACT

Accumulating evidence suggests that natural bioactive compounds, alone or in combination with traditional chemotherapeutic agents, could be used as potential therapies to fight cancer. In this study, we employed four natural bioactive compounds (curcumin, resveratrol, melatonin, and silibinin) and studied their role in redox control and ability to promote apoptosis in androgen sensitive and insensitive prostate cancer cells. Here is shown that curcumin and resveratrol promote ROS production and induce apoptosis in LNCaP and PC-3. An increase in reactive species is a trigger event in curcumin-induced apoptosis and a consequence of resveratrol effects on other pathways within these cells. Moreover, here we demonstrated that these four compounds affect differently one of the main intracellular redox regulator, the thioredoxin system. Exposure to curcumin and resveratrol promoted TRX1 oxidation and altered its subcellular location. Furthermore, resveratrol diminished TRX1 levels in PC-3 cells and increased the expression of its inhibitor TXNIP. Conversly, melatonin and silibinin only worked as cytostatic agents, reducing ROS levels and showing preventive effects against TRX oxidation. All together, this work explores the effect of compounds currently tested as chemo-preventive agents in prostate cancer therapy, on the TRX1 redox state and function. Our work shows the importance that the TRX system might have within the differences found in their mechanisms of action. These bioactive compounds trigger different responses and affect ROS production and redox systems in prostate cancer cells, suggesting the key role that redox-related pathways might play in processes like differentiation or survival in prostate cancer.

No MeSH data available.


Related in: MedlinePlus