Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model

Ochoa-Callejero, Laura; Pérez‐Martínez, Laura; Rubio-Mediavilla, Susana; Oteo, José A.; Martı́nez, Alfredo; Blanco, José Ramón

doi:10.1371/journal.pone.0053992

Cited by 81 publications

(73 citation statements)

References 50 publications

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“…In recent years, MVC was also assessed for its potential as antineoplastic agent in a variety of primary and metastatic cancers. In this regard, animal models have been used to study the impact [31][32][33]. Promising outcomes from these cancer-related studies (other than CRC) involving MVC as a CCR5 blocker provoked us to study the effects of this antagonist in CRC cells.…”

Section: Discussionmentioning

confidence: 99%

CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells

et al. 2015

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Alterations in the expression of C-C chemokine receptor type 5 (CCR5 or CD195) have been correlated with disease progression in different cancers. Recently, a few investigations have reported the blockage of this receptor by an antagonist (maraviroc) and its antineoplastic effects on tumor cell growth. However, little is known about the mechanistic reasons behind these antineoplastic effects of CCR5 blockage by maraviroc. In this study, we blocked the CCR5 receptor by maraviroc in SW480 and SW620 colorectal cancer cells to study the resulting changes in biological properties and related pathways. This blockage induced significantly reduced proliferation and a profound arrest in G1 phase of the cell cycle. Concomitantly, maraviroc caused significant signs of apoptosis at morphological level. Significant modulation of multiple apoptosis-relevant genes was also noticed at mRNA levels. In addition, we found remarkable increases in cleaved caspases at protein level. These modulations led us to propose a signaling pathway for the observed apoptotic effects. In conclusion, blocking the CCR5 by maraviroc induces significant cytotoxic and apoptotic effects in colorectal cancer cells. Thus, maraviroc can be considered a model compound, which may foster the development of further CCR5 antagonists to be used for the treatment of colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells

et al. 2015

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“…The small molecules, maraviroc and vicriviroc, reduced the invasive abilities of breast cancer cells in vitro. Of the two compounds, maraviroc was shown to decrease pulmonary metastasis by basal breast cancer cells in vivo, and to reduce the tumor burden and prolong the survival of mice with hepatocellular carcinoma (74,78). Similarly, another small-molecule CCR5 inhibitor, TAK-779, was identified to reduce infiltration of regulatory T cells (Tregs) and to reduce tumor size in a pancreatic cancer model in vivo (79).…”

Section: Therapeutic Implications Of C-c Motif Ccrs In Gastric Cancermentioning

confidence: 99%

C‑C motif chemokine receptors in gastric cancer (Review)

et al. 2017

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Abstract. Gastric cancer is the fifth most common cancer and the third leading cause of cancer-associated mortality worldwide. Despite recent advances in molecular and clinical research, patients with gastric cancer at an advanced stage have a dismal prognosis and poor survival rates, and systemic treatment relies predominantly on traditional cytotoxic chemotherapy. To improve patients' quality of life and survival, an improved understanding of the complex molecular mechanisms involved in gastric cancer progression and treatment resistance, and of its clinical application in the development of novel targeted therapies, is urgently required. Chemokines are a group of small chemotactic cytokines that interact with seven-transmembrane G-protein-coupled receptors, and this interaction serves a crucial role in various physiological processes, including organ development and the host immune response, to recruit cells to specific sites in the body. There is also accumulating evidence that chemokines and chemokine receptors (CCRs) contribute to tumor development and progression, as well as metastasis. However, research regarding the functional roles of chemokines and their receptors in cancer is dynamic and context-dependent, and much remains to be elucidated, although various aspects have been explored extensively. In gastric cancer, C-C motif CCRs are involved in the biological behavior of tumor cells, including the processes of growth, invasion and survival, as well as the epithelial-mesenchymal transition. In the present review, attention is given to the clinical relevance of C-C motif CCRs in the development, progression, and metastasis of gastric cancer, particularly CCR7 and CCR5, which have been investigated extensively, as well as their potential therapeutic implications.

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“…Upon liver injury CCL5 chemokine strongly expressed to recruit inflammatory cells and HSC. Inhibition of CCL5 either through Met-RANTES or maraviroc interferes with HSC migration and their activation, and enhances survivability of hepatocytes in mice [24,25]. Galectin-3 inhibitors GR-MD-02 and GM-CT-01 are also promising candidate in the race of antifibrotic drug in reversing established severe fibrosis and cirrhosis [26].…”

Section: Deactivation or Elimination Of Activated Hepatic Stellate Cellsmentioning

confidence: 99%

Hepatic Fibrosis and its Regression: The Pursuit of Treatment

Biswas¹,

Sharma²

2016

JLRDT

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Excessive hepatic fibrosis leading towards the cirrhosis is the major determinant of morbidity and mortality in chronic liver disease patients. The reversing hepatic fibrosis has been intensively studied and fuelled up the hope in development of effective and targeted antifibrotic therapy in upcoming years. There are four pillars of pharmacological approach in regression of fibrosis-cessation of damage, the changes in pro-fibrogenic microenvironment, deactivation of activated hepatic stellate cells and degradation of ECM. In this review, we are going to discuss therapeutic concepts and estimate the leading candidate antifibrotic therapy to be introduced in the intervention of hepatic fibrosis.

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Maraviroc, a CCR5 Antagonist, Prevents Development of Hepatocellular Carcinoma in a Mouse Model

Cited by 81 publications

References 50 publications

CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells

CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells

C‑C motif chemokine receptors in gastric cancer (Review)

Hepatic Fibrosis and its Regression: The Pursuit of Treatment

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