Resveratrol integrates metabolic and growth effects in PC3 prostate cancer cells‑involvement of prolyl hydroxylase and hypoxia inducible factor‑1

Fonseca, João; Moradi, Fereshteh; Maddalena, Lucas A.; Ferreira‐Tollstadius, Bruna; Selim, Shehab; Stuart, Jeffrey A.

doi:10.3892/ol.2018.9526

Cited by 18 publications

(18 citation statements)

References 34 publications

(33 reference statements)

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“…In prostate cancer cells, resveratrol supplementation induces apoptosis and cell cycle arrest by shifting cellular metabolism from glycolysis into mitochondrial oxidative phosphorylation. Resveratrol improves mitochondrial biogenesis, fusion and respiration by HIF-1α down-regulation to stimulate cell cycle arrest in cancer cells [220]. These studies highlight the fact that resveratrol is able to target cellular metabolism of cancer cells and by enhancing oxidative phosphorylation predisposes cancer cells into apoptosis.…”

Section: Resveratrol Glycolysis and Mitochondrial Oxidative Phosphormentioning

confidence: 77%

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

et al. 2020

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Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy.

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Section: Resveratrol Glycolysis and Mitochondrial Oxidative Phosphormentioning

confidence: 77%

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

et al. 2020

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“…This article provides an overview of recent findings about the anti-PCa activity of different natural compounds (Figure 2, Table 1). [47][48][49][50][51][52][53][54]80,100,107,123,124,[135][136][137][138][139]161,163,164,186,190,191,212] The use of phytochemicals for PCa management offers several advantages. Firstly, natural products are safe and well tolerated, as well as usually economically affordable.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, treatments aimed at blocking these pathways and/or shifting lactic acid fermentation towards mitochondrial oxidative phosphorylation have shown promise in reducing tumor growth [189]. In recent studies by Fonseca J et al, resveratrol was found to promote a shift towards mitochondrial oxidation in PCa cells concomitantly with the suppression of proliferation, and when this change was prevented by culturing tumor cells in glucose-free medium or via prolyl hydroxylase (PHD) inhibition-mediated stabilization of HIF-1α, the phenol did not affect oxidative phosphorylation and cell growth, indicating that the metabolic shift from glucose fermentation to oxidation is fundamental for its anti-cancer effects [190,191].…”

Section: Natural Compounds Impairing Metabolismmentioning

confidence: 97%

Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets

Fontana

Raimondi

Marzagalli

et al. 2020

Cells

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Prostate cancer (PCa) represents a major cause of cancer mortality among men in developed countries. Patients with recurrent disease initially respond to androgen-deprivation therapy, but the tumor eventually progresses into castration-resistant PCa; in this condition, tumor cells acquire the ability to escape cell death and develop resistance to current therapies. Thus, new therapeutic approaches for PCa management are urgently needed. In this setting, natural products have been extensively studied for their anti-PCa activities, such as tumor growth suppression, cell death induction, and inhibition of metastasis and angiogenesis. Additionally, numerous studies have shown that phytochemicals can specifically target the androgen receptor (AR) signaling, as well as the PCa stem cells (PCSCs). Interestingly, many clinical trials have been conducted to test the efficacy of nutraceuticals in human subjects, and they have partially confirmed the promising results obtained in vitro and in preclinical models. This article summarizes the anti-cancer mechanisms and therapeutic potentials of different natural compounds in the context of PCa prevention and treatment.

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“…Indeed, resveratrol (20 mg/kg of body weight) also decreases mRNA and protein levels of HIF‐1α in the liver of rats induced to an ischemia/reperfusion (Zhang, Li, Yu, & Wu, ). Interestingly, PC3 prostate cancer cells carrying a mutant HIF‐1α lacking prolines 402 and 564 did not display any effect with resveratrol supplementation (10 µM) on mitochondrial fusion, biogenesis, respiration or cell growth at high glucose levels (25 mM), as the wild type cells did (Fonseca et al, ). Indeed, the effects of resveratrol with the mutant HIF‐1α at high glucose are similar to the effects observed with resveratrol and galactose (which only generates ATP through OXPHOS) (Fonseca et al, ), which suggests a possible association among mitochondrial respiration, resveratrol, and HIF‐1α activity.…”

Section: The Relationship Between the Cytotoxic Effect Of Resveratrolmentioning

confidence: 98%

“…Interestingly, PC3 prostate cancer cells carrying a mutant HIF‐1α lacking prolines 402 and 564 did not display any effect with resveratrol supplementation (10 µM) on mitochondrial fusion, biogenesis, respiration or cell growth at high glucose levels (25 mM), as the wild type cells did (Fonseca et al, ). Indeed, the effects of resveratrol with the mutant HIF‐1α at high glucose are similar to the effects observed with resveratrol and galactose (which only generates ATP through OXPHOS) (Fonseca et al, ), which suggests a possible association among mitochondrial respiration, resveratrol, and HIF‐1α activity. In addition, it has been reported that the resveratrol (10 µM) effects on hydrogen peroxide release, cell growth and the mitochondrial network in C2C12 mouse myoblasts and PC3 human prostate cancer cells are dependent on oxygen levels (5% and 18%) and glucose concentrations (5 and 25 mM) (Fonseca, Moradi, Valente, & Stuart, ).…”

Section: The Relationship Between the Cytotoxic Effect Of Resveratrolmentioning

confidence: 98%

Resveratrol cytotoxicity is energy‐dependent

2019

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Resveratrol is a phytochemical that may promote health. However, it has also been reported to be a toxic compound. The molecular mechanism by which resveratrol acts remains unclear. The inhibition of the oxidative phosphorylation (OXPHOS) pathway appears to be the molecular mechanism of resveratrol. Taking this into account, we propose that the cytotoxic properties of resveratrol depend on the energy (e.g., carbohydrates, lipids, and proteins) availability in the cells. In this regard, in a condition with low energy accessibility, resveratrol could enhance ATP starvation to lethal levels. In contrast, when cells are supplemented with high quantities of energy and resveratrol, the inhibition of OXPHOS might produce a low‐energy environment, mimicking the beneficial effects of caloric restriction. This review suggests that investigating a possible complex relationship between caloric intake and the differential effects of resveratrol on OXPHOS may be justified. Practical applications A low‐calorie diet accompanied by significant levels of resveratrol might modify cellular bioenergetics, which could impact cellular viability and enhance the anti‐cancer properties of resveratrol.

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Resveratrol integrates metabolic and growth effects in PC3 prostate cancer cells‑involvement of prolyl hydroxylase and hypoxia inducible factor‑1

Cited by 18 publications

References 34 publications

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

Natural Compounds in Prostate Cancer Prevention and Treatment: Mechanisms of Action and Molecular Targets

Resveratrol cytotoxicity is energy‐dependent

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