Tempol effect on oxidative and mitochondrial markers in preclinical models for prostate cancer.

Background: Tempol is a redox-cycling nitroxide considered a potent antioxidant. The present study investigated the tempol effects on oxidative stress and mitochondrial markers on prostate cancer (PCa). Methods: PC-3 and LnCaP cells were exposed to tempol. Cell viability test, western blot and Amplex Red analyses were performed. In vivo, five experimental groups evaluated tempol effects in the early (CT12 and TPL12 groups) and late stages (CT20, TPL20-I, and TLP20-II) of PCa development. The TPL groups were treated with 50 or 100 mg/kg tempol doses. Control groups received water as the vehicle. The ventral lobe of the prostate and the blood were collected and submitted to western blotting or enzymatic activity analyses. Results: In vitro, tempol decreased cell viability and differentially altered the H2O2 content for PC-3 and LNCaP. Tempol increased SOD2 levels in both cell lines and did not alter Catalase protein levels. In vivo, tempol increased SOD2 levels in the early stage and did not change Catalase levels in the different PCa stages. Systemically, tempol decreased SOD2 levels in the late-stage and improved redox status in the early and late stages, which was confirmed by reduced LDH in tempol groups. Alterations on energetic metabolism and oxidative phosphorylation were observed in TRAMP model. Conclusion: Tempol can be considered a beneficial therapy for PCa treatment considering its antioxidant and low toxicity properties, however the PCa progression must be evaluated to get successful therapy.

Differential tempol effects in prostatic cancer: angiogenesis and short- and long-term treatments.

Prostate cancer (PCa) is the second cause of cancer death among men worldwide. Several processes are involved in the development and progression of PCa such as angiogenesis, inflammation and oxidative stress. The present study investigated the effect of short- or long-term Tempol treatment at different stages of prostate adenocarcinoma progression, focusing on angiogenic, proliferative, and stromal remodeling processes in TRAMP mice. The dorsolateral lobe of the prostate of TRAMP mice were evaluated at two different stages of PCa progression; early and late stages. Early stage was again divided into, short- or long-term. 50 mg/kg Tempol dose was administered orally. The results demonstrated that Tempol mitigated the prostate histopathological lesion progressions in the TRAMP mice in all treated groups. However, Tempol increased molecules involved in the angiogenic process such as CD31 and VEGFR2 relative frequencies, particularly in long-term treatment. In addition, Tempol upregulated molecule levels involved in angiogenesis and stromal remodeling process VEGF, TGF-ß1, VE-cadherin and vimentin, particularly, in T8-16 group. Thus, it was concluded that Tempol treatment delayed prostatic lesion progression in the dorsolateral lobe of the TRAMP mice. However, Tempol also led to pro-angiogenic effects and glandular stromal microenvironment imbalance, especially, in the long-term treatment.

Brazilian Berry Extract Differentially Induces Inflammatory and Immune Responses in Androgen Dependent and Independent Prostate Cancer Cells.

Jaboticaba is a Brazilian berry, which is rich in fibers and bioactive compounds and shows high antioxidant and antiproliferative activities. Prostate cancer (PCa) is the second most common type of cancer among men and its progression is influenced by androgens and inflammation. Previous studies reported the ability of the jaboticaba to modulate pathways involved in prostate diseases. The main objective of this study was to provide significant data about molecular targets of the jaboticaba peel extract (JPE) and its mechanisms of action in PCa cell lines with different androgenic status (LNCaP and PC-3). The results showed that JPE was able to decrease cell viability in both cell lines. LNCaP showed more sensitivity to JPE exposure, indicating the efficacy of the JPE treatment in terms of androgen responsiveness. JPE showed a distinct hormone dependent effect on the NF-κB signaling, with reduced NF-κB levels for LNCaP and increased NF-κB levels in PC-3 cells. Mechanisms related to cell death by apoptosis were stimulated after the JPE treatment, modulating B-cell lymphoma 2 and BAX for LNCaP and PC-3. Particularly for PC-3, the JPE treatment resulted in cytokine-cytokine receptor interaction activation mostly by up regulating pro-inflammatory, pro-angiogenic, immunostimulatory and immunosuppressive genes. Also, a set of genes related to angiogenesis and metastasis were down-regulated by JPE. In conclusion, JPE exerted an antitumor effect on PCa for both cell lines which can be enhanced if androgenic reliance is considered.