18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Munirathinam, Gnanasekar

doi:10.3892/ijo.2011.1061

Cited by 48 publications

(26 citation statements)

References 46 publications

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“…Studies comparing anti-cancer effects of Glycyrrhizin and its aglycon, Glycyrrhetinic acid (GA), in proliferation assays with murine melanoma cell line, found GA to be substantially more potent than its origin substance [23]. GA also presented anti-proliferative effects in leukemia [24] and human ovarian cancer cell lines [25], and was shown to target prostate cancer cells via an anti-inflammatory pathway through downregulation of HMGB1, IL-6 and IL-8 [26]. However, the compound has poor water solubility [27], thus presenting a pharmacological disadvantage.…”

Section: Discussionmentioning

confidence: 99%

High mobility group box 1 antagonist limits metastatic seeding in the lungs via reduction of cell-cell adhesion

et al. 2017

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Metastatic spread is the leading cause for cancer-related mortality, with the lungs being a major site for metastatic seeding. Available therapies for patients with metastatic disease are extremely limited. Therefore, there is a desperate need for new strategies to prevent or limit metastatic dissemination and treat existing metastases. The metastatic cascade is highly complex and is affected by multiple factors related to both tumor cells themselves and the microenvironment in the future site of metastasis. We hypothesized that modifying the lung microenvironment by blocking central ubiquitous signals may affect metastatic seeding in the lungs. Given the high basal levels of the Receptor for Advanced Glycation End products (RAGE) in the pulmonary tissue, and its pro-inflammatory properties, we investigated the consequences of interfering with its ligand; High Mobility Group Box 1 (HMGB1). To this end, we tested the effect of Carbenoxolone, an HMGB1 antagonist, on primary tumor growth and metastatic progression in several murine tumor models. We show that antagonizing HMGB1 prevents the adhesion and colonization of cancer cells in the lungs through the reduction of their adhesion and cell–cell interaction both in vitro and in vivo. We demonstrated that these activities are mediated by downregulation of the adhesion molecule Intercellular Adhesion Molecule 1 (ICAM1) and ultimately result in reduced metastatic burden. Carbenoxolone decreases significantly lung metastases formation and can be used potentially as prophylactic therapy for metastatic diseases.

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Section: Discussionmentioning

confidence: 99%

High mobility group box 1 antagonist limits metastatic seeding in the lungs via reduction of cell-cell adhesion

et al. 2017

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“…HMGB1 is highly expressed in PCa cells92 and targeting HMGB1 disrupts tumor progression by inhibiting activation of T-cells and reducing infiltration of macrophages which are considered to be key inflammatory cells in promoting variety of cancers including PCa 93. Interestingly, androgen deprivation caused HMG1's secretion in prostatic stromal cells supporting the notion that deprivation therapy may upregulate the expression of HMGB1 leading to either hormone resistance or metastatic disease 94…”

Section: Inflammationmentioning

confidence: 95%

Molecular signaling involving intrinsically disordered proteins in prostate cancer

et al. 2016

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Investigations on cellular protein interaction networks (PINs) reveal that proteins that constitute hubs in a PIN are notably enriched in Intrinsically Disordered Proteins (IDPs) compared to proteins that constitute edges, highlighting the role of IDPs in signaling pathways. Most IDPs rapidly undergo disorder-to-order transitions upon binding to their biological targets to perform their function. Conformational dynamics enables IDPs to be versatile and to interact with a broad range of interactors under normal physiological conditions where their expression is tightly modulated. IDPs are involved in many cellular processes such as cellular signaling, transcriptional regulation, and splicing; thus, their high-specificity/low-affinity interactions play crucial roles in many human diseases including cancer. Prostate cancer (PCa) is one of the leading causes of cancer-related mortality in men worldwide. Therefore, identifying molecular mechanisms of the oncogenic signaling pathways that are involved in prostate carcinogenesis is crucial. In this review, we focus on the aspects of cellular pathways leading to PCa in which IDPs exert a primary role.

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“…While surgery, androgen ablation and radiation therapy are effective treatments of prostate cancer, cases commonly progress to a hormone independent state. The current standard of treatment in advanced, hormone-refractory prostate cancer is unsatisfactory [2]. New modalities of treatment are, therefore, needed.…”

Section: Introductionmentioning

confidence: 99%

Hepatoma-derived growth factor: A survival-related protein in prostate oncogenesis and a potential target for vitamin K2

Shetty

Dasari

Banerjee

et al. 2016

Urologic Oncology: Seminars and Original Investigations

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Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor which has previously been shown to be expressed in a variety of cancers. HDGF over-expression has also previously been correlated with a poor prognosis in several cancers. The significance of HDGF in prostate cancer, however, has not been investigated. Here, we show that HDGF is over-expressed in both androgen-sensitive LNCaP cells and androgen-insensitive DU145, 22RV1 and PC-3 cells. Forced over-expression enhanced cell viability of RWPE-1 cells, while HDGF knockdown reduced cell proliferation in human prostate cancer cells. We also show that HDGF may serve as a survival related protein as ectopic over-expression of HDGF in RWPE cells up-regulated the expression of anti-apoptosis proteins cyclin E and BCL-2, while simultaneously down-regulating pro-apoptotic protein BAX. Western blot analysis also showed that HDGF over-expression modulated the activity of phospho AKT as well as NF-kB, and these results correlated with in vitro migration and invasion assays. We next assessed the therapeutic potential of HDGF inhibition with a HDGF monoclonal antibody and vitamin k2, showing reduced cell proliferation as well as inhibition of NF-kB expression in HDGF over-expressed RWPE cells treated with a HDGF monoclonal antibody and vitamin K2. Collectively, our results suggest that HDGF is a relevant protein in prostate oncogenesis and may serve as a potential therapeutic target in prostate cancer.

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18α-glycyrrhetinic acid targets prostate cancer cells by down-regulating inflammation-related genes

Cited by 48 publications

References 46 publications

High mobility group box 1 antagonist limits metastatic seeding in the lungs via reduction of cell-cell adhesion

High mobility group box 1 antagonist limits metastatic seeding in the lungs via reduction of cell-cell adhesion

Molecular signaling involving intrinsically disordered proteins in prostate cancer

Hepatoma-derived growth factor: A survival-related protein in prostate oncogenesis and a potential target for vitamin K2

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