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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Melatonin and Docosahexaenoic Acid Decrease Proliferation of PNT1A Prostate Benign Cells via Modulation of Mitochondrial Bioenergetics and ROS Production

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Author(s):
Tamarindo, Guilherme H. [1] ; Ribeiro, Daniele L. [2] ; Gobbo, Marina G. [3] ; Guerra, Luiz H. A. [3] ; Rahal, Paula [3] ; Taboga, Sebastiao R. [3] ; Gadelha, Fernanda R. [4] ; Goes, Rejane M. [3]
Total Authors: 8
Affiliation:
[1] Univ Estadual Campinas, Inst Biol, Campinas, SP - Brazil
[2] Univ Fed Uberlandia, Inst Biomed Sci, Dept Histol, Uberlandia, MG - Brazil
[3] Sao Paulo State Univ, Inst Biosci Humanities & Exact Sci, Dept Biol, Sao Jose Do Rio Preto, SP - Brazil
[4] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Campinas, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY; 2019.
Web of Science Citations: 2
Abstract

Prostate cancer development has been associated with changes in mitochondria' activity and reactive oxygen species (ROS) production. Melatonin (MLT) and docosahexaenoic acid (DHA) have properties to modulate both, but their protective role, mainly at early stages of prostate cancer, remains unclear. In this study, the effects of MLT and DHA, combined or not, on PNT1A cells with regard to mitochondria bioenergetics, ROS production, and proliferation-related pathways were examined. Based on dose response and lipid accumulation assays, DHA at 100 mu M and MLT at 1 mu M for 48 h were chosen. DHA doubled and MLT reduced (40%) superoxide anion production, but coincubation (DM) did not normalize to control. Hydrogen peroxide production decreased after MLT incubation only (p < 0.01). These alterations affected the area and perimeter of mitochondria, since DHA increased whereas MLT decreased, but such hormone has no effect on coincubation. DHA isolated did not change the oxidative phosphorylation rate (OXPHOS), but decreased (p < 0.001) the mitochondria' bioenergetic reserve capacity (MBRC) which is closely related to cell responsiveness to stress conditions. MLT, regardless of DHA, ameliorated OXPHOS and recovered MBRC after coincubation. All incubations decreased AKT phosphorylation; however, only MLT alone inhibited p-mTOR. MLT increased p-ERK1/2 and, when combined to DHA, increased GSTP1 expression (p < 0.01). DHA did not change the testosterone levels in the medium, whereas MLT alone or coincubated decreased by about 20%; however, any incubation affected AR expression. Moreover, incubation with luzindole revealed that MLT effects were MTR1/2-independent. In conclusion, DHA increased ROS production and impaired mitochondrial function which was probably related to AKT inactivation; MLT improved OXPHOS and decreased ROS which was related to AKT/mTOR dephosphorylation, and when coincubated, the antiproliferative action was related to mitochondrial bioenergetic modulation associated to AKT and ERK1/2 regulation. Together, these findings point to the potential application of DHA and MLT towards the prevention of proliferative prostate diseases. (AU)

FAPESP's process: 15/24595-9 - Correlation between the biochemical parameters of Trypanosoma cruzi isolates from Chagas disease patients with different clinical forms of the disease and the pathogenesis of the disease
Grantee:Fernanda Ramos Gadelha
Support type: Regular Research Grants
FAPESP's process: 13/16368-7 - Influence of exogen melatonin on rat prostate tissue response to experimental diabetes and interference on androgen and insulin actions
Grantee:Rejane Maira Góes
Support type: Regular Research Grants
FAPESP's process: 15/13371-2 - Evaluation of mitochondrial bioenergetics and oxidative stress in human prostate cells treated with docosahexaenoic acid and melatonin
Grantee:Guilherme Henrique Tamarindo
Support type: Scholarships in Brazil - Master