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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.


Effect of curcumin and resveratrol on ASK1-overexpressed cells viability. LNCaP and PC-3 cells were transiently transfected with vector pcDNA3.1 (MOCK), wild-type ASK1 (ASK1) or kinase inactive mutant (KM-ASK1). Cells were set overnight and then treated with 25 µM curcumin (A) or 50 µM resveratrol (B). Cell viability was studied using MTT assay after 24 treatment. Data are shown as mean±S.E.M. of 6 independent samples. *p<0.05; **p<0.01; ***p<0.001 versus CON. PC-3 cells (C) transiently transfected with vector, ASK1 or KM-ASK1 were incubated with or without curcumin (25 µM) for 24 h. Apoptosis was evaluated after staining with Annexin V/PI by flow cytometry.
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f0025: Effect of curcumin and resveratrol on ASK1-overexpressed cells viability. LNCaP and PC-3 cells were transiently transfected with vector pcDNA3.1 (MOCK), wild-type ASK1 (ASK1) or kinase inactive mutant (KM-ASK1). Cells were set overnight and then treated with 25 µM curcumin (A) or 50 µM resveratrol (B). Cell viability was studied using MTT assay after 24 treatment. Data are shown as mean±S.E.M. of 6 independent samples. *p<0.05; **p<0.01; ***p<0.001 versus CON. PC-3 cells (C) transiently transfected with vector, ASK1 or KM-ASK1 were incubated with or without curcumin (25 µM) for 24 h. Apoptosis was evaluated after staining with Annexin V/PI by flow cytometry.

Mentions: In order to evaluate indirectly the participation of ASK1 in prostate cancer survival, LNCaP and PC-3 cells were transfected with hASK1-HA-pcDNA3 or the kinase mutant hASK1-KM-HApcDNA3 and cell viability was assessed after treatment with curcumin and resveratrol by MTT assay (Fig. 5A, B).


Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells
Effect of curcumin and resveratrol on ASK1-overexpressed cells viability. LNCaP and PC-3 cells were transiently transfected with vector pcDNA3.1 (MOCK), wild-type ASK1 (ASK1) or kinase inactive mutant (KM-ASK1). Cells were set overnight and then treated with 25 µM curcumin (A) or 50 µM resveratrol (B). Cell viability was studied using MTT assay after 24 treatment. Data are shown as mean±S.E.M. of 6 independent samples. *p<0.05; **p<0.01; ***p<0.001 versus CON. PC-3 cells (C) transiently transfected with vector, ASK1 or KM-ASK1 were incubated with or without curcumin (25 µM) for 24 h. Apoptosis was evaluated after staining with Annexin V/PI by flow cytometry.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5385622&req=5

f0025: Effect of curcumin and resveratrol on ASK1-overexpressed cells viability. LNCaP and PC-3 cells were transiently transfected with vector pcDNA3.1 (MOCK), wild-type ASK1 (ASK1) or kinase inactive mutant (KM-ASK1). Cells were set overnight and then treated with 25 µM curcumin (A) or 50 µM resveratrol (B). Cell viability was studied using MTT assay after 24 treatment. Data are shown as mean±S.E.M. of 6 independent samples. *p<0.05; **p<0.01; ***p<0.001 versus CON. PC-3 cells (C) transiently transfected with vector, ASK1 or KM-ASK1 were incubated with or without curcumin (25 µM) for 24 h. Apoptosis was evaluated after staining with Annexin V/PI by flow cytometry.
Mentions: In order to evaluate indirectly the participation of ASK1 in prostate cancer survival, LNCaP and PC-3 cells were transfected with hASK1-HA-pcDNA3 or the kinase mutant hASK1-KM-HApcDNA3 and cell viability was assessed after treatment with curcumin and resveratrol by MTT assay (Fig. 5A, B).

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.