Limits...
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

Effect of curcumin and resveratrol on TRX1, TRXR1 and TXNIP mRNA levels and enzymatic activities in prostate cancer cells. LNCaP and PC-3 cells were incubated with 25 µM curcumin or 50 µM resveratrol for 48 h. Trx1 and TrxR1mRNA levels in LNCaP (A) and PC-3 (B) were analyzed by RT-qPCR. TRX (C) and TRXR (D) enzymatic activities were analyzed in LNCaP and PC-3 cells after 25 µM curcumin or 50 µM resveratrol for 48 h. Txnip mRNA levels (E) were analyzed by RT-qPCR. Graphs represent the mean ±SEM obtained from three independent experiments performed in triplicates. *p<0.05; #p<0.01; ***p<0.001 versus CON.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5385622&req=5

f0035: Effect of curcumin and resveratrol on TRX1, TRXR1 and TXNIP mRNA levels and enzymatic activities in prostate cancer cells. LNCaP and PC-3 cells were incubated with 25 µM curcumin or 50 µM resveratrol for 48 h. Trx1 and TrxR1mRNA levels in LNCaP (A) and PC-3 (B) were analyzed by RT-qPCR. TRX (C) and TRXR (D) enzymatic activities were analyzed in LNCaP and PC-3 cells after 25 µM curcumin or 50 µM resveratrol for 48 h. Txnip mRNA levels (E) were analyzed by RT-qPCR. Graphs represent the mean ±SEM obtained from three independent experiments performed in triplicates. *p<0.05; #p<0.01; ***p<0.001 versus CON.

Mentions: In order to confirm whether curcumin and resveratrol treatment modified TRX1 and TRXR1 activities or their mRNA levels, they were analyzed after 48 h of exposure to the compounds in both cell lines. Curcumin and resveratrol incubation increased TRX1 and TRXR1 transcription in LNCaP cells (Fig. 7A). On the other hand, curcumin increased TRXR1 mRNA levels but no significant differences were found in TRX1. Resveratrol dramatically decreased TRX1 transcription while significantly increased TRXR1 mRNA levels in PC-3 cells (Fig. 7B). No differences were found in total TRX1 activity, at the concentrations employed, neither in LNCaP nor in PC-3 cells treated with curcumin or resveratrol (Fig. 8C). However, TRXR1 activity was significantly decreased after curcumin treatment in LNCaP cells (Fig. 7D).


Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells
Effect of curcumin and resveratrol on TRX1, TRXR1 and TXNIP mRNA levels and enzymatic activities in prostate cancer cells. LNCaP and PC-3 cells were incubated with 25 µM curcumin or 50 µM resveratrol for 48 h. Trx1 and TrxR1mRNA levels in LNCaP (A) and PC-3 (B) were analyzed by RT-qPCR. TRX (C) and TRXR (D) enzymatic activities were analyzed in LNCaP and PC-3 cells after 25 µM curcumin or 50 µM resveratrol for 48 h. Txnip mRNA levels (E) were analyzed by RT-qPCR. Graphs represent the mean ±SEM obtained from three independent experiments performed in triplicates. *p<0.05; #p<0.01; ***p<0.001 versus CON.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385622&req=5

f0035: Effect of curcumin and resveratrol on TRX1, TRXR1 and TXNIP mRNA levels and enzymatic activities in prostate cancer cells. LNCaP and PC-3 cells were incubated with 25 µM curcumin or 50 µM resveratrol for 48 h. Trx1 and TrxR1mRNA levels in LNCaP (A) and PC-3 (B) were analyzed by RT-qPCR. TRX (C) and TRXR (D) enzymatic activities were analyzed in LNCaP and PC-3 cells after 25 µM curcumin or 50 µM resveratrol for 48 h. Txnip mRNA levels (E) were analyzed by RT-qPCR. Graphs represent the mean ±SEM obtained from three independent experiments performed in triplicates. *p<0.05; #p<0.01; ***p<0.001 versus CON.
Mentions: In order to confirm whether curcumin and resveratrol treatment modified TRX1 and TRXR1 activities or their mRNA levels, they were analyzed after 48 h of exposure to the compounds in both cell lines. Curcumin and resveratrol incubation increased TRX1 and TRXR1 transcription in LNCaP cells (Fig. 7A). On the other hand, curcumin increased TRXR1 mRNA levels but no significant differences were found in TRX1. Resveratrol dramatically decreased TRX1 transcription while significantly increased TRXR1 mRNA levels in PC-3 cells (Fig. 7B). No differences were found in total TRX1 activity, at the concentrations employed, neither in LNCaP nor in PC-3 cells treated with curcumin or resveratrol (Fig. 8C). However, TRXR1 activity was significantly decreased after curcumin treatment in LNCaP cells (Fig. 7D).

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