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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.


Influence of bioactive compounds on TRX1 levels, subcellular localization and redox state. LNCaP (A, C) and PC-3 (B, D) cells were treated with 1 mM melatonin, 50 µM silibinin, 25 µM curcumin or 50 µM resveratrol for 48 h and TRX1 protein levels were evaluated by western blot. HDAC2 and β-Actin were employed as loading controls. Redox state of TRX1 in LNCaP (E) and PC-3 (F) was analyzed after 48 h of treatment. Experiments were repeated at least 3 times and data of a representative experiment is shown.
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f0030: Influence of bioactive compounds on TRX1 levels, subcellular localization and redox state. LNCaP (A, C) and PC-3 (B, D) cells were treated with 1 mM melatonin, 50 µM silibinin, 25 µM curcumin or 50 µM resveratrol for 48 h and TRX1 protein levels were evaluated by western blot. HDAC2 and β-Actin were employed as loading controls. Redox state of TRX1 in LNCaP (E) and PC-3 (F) was analyzed after 48 h of treatment. Experiments were repeated at least 3 times and data of a representative experiment is shown.

Mentions: Since TRX1 is the major redox regulator of ASK1, we evaluated the effect of melatonin, silibinin, curcumin and resveratrol on TRX1 protein levels, subcellular location and redox state. Total protein levels of TRX1 in LNCaP and PC-3 are shown in Fig. 6A and 6B, respectively. Melatonin, silibinin and curcumin induced an increase in TRX1 in both cell lines, while resveratrol displayed different effects in androgen-sensitive and insensitive cells. Therefore, incubation with the stilbene caused an increase in TRX1 protein levels in LNCaP but a significant decrease in PC-3 cells (Fig. 6A and B). Because TRX1 translocates into the nucleus under oxidative stress, we analyzed its subcellular location after 48 h incubation with the four compounds. Following incubation with melatonin and silibinin, no significant differences were found in TRX1 location in LNCaP (Fig. 6C), although both clearly decreased nuclear TRX1 levels in the androgen-independent cells (Fig. 6D). Curcumin significantly induced nuclear TRX1 translocation in both cell types while resveratrol promoted an increase in its nuclear localization in LNCaP, but dramatically decreased protein levels in both compartments in PC-3 cells, consistent with the results mentioned above (Fig. 6B).


Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells
Influence of bioactive compounds on TRX1 levels, subcellular localization and redox state. LNCaP (A, C) and PC-3 (B, D) cells were treated with 1 mM melatonin, 50 µM silibinin, 25 µM curcumin or 50 µM resveratrol for 48 h and TRX1 protein levels were evaluated by western blot. HDAC2 and β-Actin were employed as loading controls. Redox state of TRX1 in LNCaP (E) and PC-3 (F) was analyzed after 48 h of treatment. Experiments were repeated at least 3 times and data of a representative experiment is shown.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0030: Influence of bioactive compounds on TRX1 levels, subcellular localization and redox state. LNCaP (A, C) and PC-3 (B, D) cells were treated with 1 mM melatonin, 50 µM silibinin, 25 µM curcumin or 50 µM resveratrol for 48 h and TRX1 protein levels were evaluated by western blot. HDAC2 and β-Actin were employed as loading controls. Redox state of TRX1 in LNCaP (E) and PC-3 (F) was analyzed after 48 h of treatment. Experiments were repeated at least 3 times and data of a representative experiment is shown.
Mentions: Since TRX1 is the major redox regulator of ASK1, we evaluated the effect of melatonin, silibinin, curcumin and resveratrol on TRX1 protein levels, subcellular location and redox state. Total protein levels of TRX1 in LNCaP and PC-3 are shown in Fig. 6A and 6B, respectively. Melatonin, silibinin and curcumin induced an increase in TRX1 in both cell lines, while resveratrol displayed different effects in androgen-sensitive and insensitive cells. Therefore, incubation with the stilbene caused an increase in TRX1 protein levels in LNCaP but a significant decrease in PC-3 cells (Fig. 6A and B). Because TRX1 translocates into the nucleus under oxidative stress, we analyzed its subcellular location after 48 h incubation with the four compounds. Following incubation with melatonin and silibinin, no significant differences were found in TRX1 location in LNCaP (Fig. 6C), although both clearly decreased nuclear TRX1 levels in the androgen-independent cells (Fig. 6D). Curcumin significantly induced nuclear TRX1 translocation in both cell types while resveratrol promoted an increase in its nuclear localization in LNCaP, but dramatically decreased protein levels in both compartments in PC-3 cells, consistent with the results mentioned above (Fig. 6B).

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.