GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cells

Cárdenas, Sofía; Colombero, Cecilia; Panelo, Laura Carolina; Dakarapu, Rambabu; Falck, John R.; Costas, Mónica Alejandra; Nowicki, Susana

doi:10.1016/j.bbalip.2019.158573

Cited by 25 publications

(30 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Several CYP1B1-mediated signaling pathways may lead to these divergent effects. For instance, while mid-chain and terminal HETEs are detrimental to the cardiovascular system [72,73], they enhance survival, proliferation, and metastasis of cancer cells [394][395][396][397][398]. Likewise, CYP1B1-mediated formation of genotoxic metabolites and DNA adducts lead to atherosclerosis and cardiovascular disease [100,101], and may also contribute to CYP1B1-mediated carcinogenesis [134].…”

Section: Discussionmentioning

confidence: 99%

CYP1B1 as a therapeutic target in cardio-oncology

2020

View full text Add to dashboard Cite

Cardiovascular complications have been frequently reported in cancer patients and survivors, mainly because of various cardiotoxic cancer treatments. Despite the known cardiovascular toxic effects of these treatments, they are still clinically used because of their effectiveness as anti-cancer agents. In this review, we discuss the growing body of evidence suggesting that inhibition of the cytochrome P450 1B1 enzyme (CYP1B1) can be a promising therapeutic strategy that has the potential to prevent cancer treatment-induced cardiovascular complications without reducing their anti-cancer effects. CYP1B1 is an extrahepatic enzyme that is expressed in cardiovascular tissues and overexpressed in different types of cancers. A growing body of evidence is demonstrating a detrimental role of CYP1B1 in both cardiovascular diseases and cancer, via perturbed metabolism of endogenous compounds, production of carcinogenic metabolites, DNA adduct formation, and generation of reactive oxygen species (ROS). Several chemotherapeutic agents have been shown to induce CYP1B1 in cardiovascular and cancer cells, possibly via activating the Aryl hydrocarbon Receptor (AhR), ROS generation, and inflammatory cytokines. Induction of CYP1B1 is detrimental in many ways. First, it can induce or exacerbate cancer treatment-induced cardiovascular complications. Second, it may lead to significant chemo/radio-resistance, undermining both the safety and effectiveness of cancer treatments. Therefore, numerous preclinical studies demonstrate that inhibition of CYP1B1 protects against chemotherapy-induced cardiotoxicity and prevents chemo- and radio-resistance. Most of these studies have utilized phytochemicals to inhibit CYP1B1. Since phytochemicals have multiple targets, future studies are needed to discern the specific contribution of CYP1B1 to the cardioprotective and chemo/radio-sensitizing effects of these phytochemicals.

show abstract

Section: Discussionmentioning

confidence: 99%

CYP1B1 as a therapeutic target in cardio-oncology

2020

View full text Add to dashboard Cite

show abstract

“…Increased production of 20-HETE in adjacent normal tissue -Induces growth and proliferation of tumor -Possibly through GPR75 pathway (Leskelä et al, 2007;Garcia et al, 2017;Caŕdenas et al, 2019) CYP4A11 w-Hydroxylases…”

Section: Lung Cancer Prostate Cancer Renal Cancer Colorectal Cancer Bmentioning

confidence: 99%

“…A series of recent studies have identified some key roles for 20-HETE in prostate cancer progression. Garcia et al first identified GPR75 as a receptor for 20-HETE (Garcia et al, 2017) and Cardenas et al demonstrated that the 20-HETE/GPR75 signaling pathways contributed to metastatic prostate cancer progression (Caŕdenas et al, 2019). Upon exposure to 20-HETE, the prostate cancer cell line PC-3 internalized GPR75, resulted in the phosphorylation of signaling molecules EGFR, NF-kB, and AKT, and altered cellular localization of AKT, NF-kB, and PKCa, all of which were reversed with the addition of GPR75 antagonist (Caŕdenas et al, 2019).…”

Section: Prostate Cancermentioning

confidence: 99%

“…While several key players have been identified, the full signaling cascade remains to be elucidated. Cardenas et al also looked at the downstream consequences of PC-3 cell exposure to 20-HETE, demonstrating that the cells exhibit prometastatic characteristics (Caŕdenas et al, 2019). Their results offer promising insight into how 20-HETE might affect prostate cancer tumor growth and progression.…”

Section: Prostate Cancermentioning

confidence: 99%

See 1 more Smart Citation

Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors

et al. 2020

View full text Add to dashboard Cite

Oxylipins derived from the oxidation of polyunsaturated fatty acids (PUFAs) act as important paracrine and autocrine signaling molecules. A subclass of oxylipins, the eicosanoids, have a broad range of physiological outcomes in inflammation, the immune response, cardiovascular homeostasis, and cell growth regulation. Consequently, eicosanoids are implicated in the pathophysiology of various diseases, most notably cancer, where eicosanoid mediated signaling is involved in tumor development, progression, and angiogenesis. Cytochrome P450s (CYPs) are a superfamily of heme monooxygenases generally involved in the clearance of xenobiotics while a subset of isozymes oxidize PUFAs to eicosanoids. Several eicosanoid forming CYPs are overexpressed in tumors, elevating eicosanoid levels and suggesting a key function in tumorigenesis and progression of tumors in the lung, breast, prostate, and kidney. This review summarizes the current understanding of CYPs' involvement in solid tumor etiology and progression providing supporting public data for gene expression from The Cancer Genome Atlas.

show abstract

“…20-HETE/GPR75 also triggered PI3K/AKT pathway to promote vascular smooth muscle cells migration, hypertrophy. Moreover, 20-HETE/GPR75 is involved in the activation of intracellular signaling in prostate cancer cells, leading to the more aggressive phenotypic differentiation of PC-3 cells ( Cárdenas et al, 2020 ). In endothelial cells, 20-HETE can promote reactive oxygen species (ROS) production through NADPH oxidase to activate the L-type Ca 2+ channel ( Medhora et al, 2008 ; Zeng et al, 2010 ; Bou-Fakhredin et al, 2021 ).…”

Section: The Roles Of Cytochrome P450 ω-Hydroxylase-mediated Eicosanoids In Inflammation-associated Diseasesmentioning

confidence: 99%

The Functions of Cytochrome P450 ω-hydroxylases and the Associated Eicosanoids in Inflammation-Related Diseases

Liu

2021

Front. Pharmacol.

View full text Add to dashboard Cite

The cytochrome P450 (CYP) ω-hydroxylases are a subfamily of CYP enzymes. While CYPs are the main metabolic enzymes that mediate the oxidation reactions of many endogenous and exogenous compounds in the human body, CYP ω-hydroxylases mediate the metabolism of multiple fatty acids and their metabolites via the addition of a hydroxyl group to the ω- or (ω-1)-C atom of the substrates. The substrates of CYP ω-hydroxylases include but not limited to arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, epoxyeicosatrienoic acids, leukotrienes, and prostaglandins. The CYP ω-hydroxylases-mediated metabolites, such as 20-hyroxyleicosatrienoic acid (20-HETE), 19-HETE, 20-hydroxyl leukotriene B4 (20-OH-LTB4), and many ω-hydroxylated prostaglandins, have pleiotropic effects in inflammation and many inflammation-associated diseases. Here we reviewed the classification, tissue distribution of CYP ω-hydroxylases and the role of their hydroxylated metabolites in inflammation-associated diseases. We described up-regulation of CYP ω-hydroxylases may be a pathogenic mechanism of many inflammation-associated diseases and thus CYP ω-hydroxylases may be a therapeutic target for these diseases. CYP ω-hydroxylases-mediated eicosanods play important roles in inflammation as pro-inflammatory or anti-inflammatory mediators, participating in the process stimulated by cytokines and/or the process stimulating the production of multiple cytokines. However, most previous studies focused on 20-HETE,and further studies are needed for the function and mechanisms of other CYP ω-hydroxylases-mediated eicosanoids. We believe that our studies of CYP ω-hydroxylases and their associated eicosanoids will advance the translational and clinal use of CYP ω-hydroxylases inhibitors and activators in many diseases.

show abstract

GPR75 receptor mediates 20-HETE-signaling and metastatic features of androgen-insensitive prostate cancer cells

Cited by 25 publications

References 52 publications

CYP1B1 as a therapeutic target in cardio-oncology

CYP1B1 as a therapeutic target in cardio-oncology

Expression and Function of Eicosanoid-Producing Cytochrome P450 Enzymes in Solid Tumors

The Functions of Cytochrome P450 ω-hydroxylases and the Associated Eicosanoids in Inflammation-Related Diseases

Contact Info

Product

Resources

About