Bromodomain‑containing proteinï¿½4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer

Wang, Yonghui; Wang, Wei; Sun, Haiyan

doi:10.3892/ijmm.2018.3642

Cited by 5 publications

(5 citation statements)

References 25 publications

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“…In addition, GA-associated targets in apoptosis have been found in various types of cancers, including TR3 in cervical cancer, 50 hERG and steroid receptor coactivator-3 (SRC-3) in leukemia, 51 , 52 BRD4 in anaplastic thyroid cancer, 53 DDIT3, DUSP1, DUSP5, GADD45B, TOP2A, TOP2B, TOP3A and ALDOA in pancreatic cancer. 8 GA could also enhance epidermal growth factor receptor (EGFR) degradation and inhibit AKT/mTOR complex 1 (mTORC1) via up-regulating AMP-activated protein kinase (AMPK)-dependent-leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) in glioma cells.…”

Section: Anti-cancer Mechanismsmentioning

confidence: 99%

Gambogic Acid as a Candidate for Cancer Therapy: A Review

Liu

Chen

Lin

et al. 2020

IJN

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Gambogic acid (GA), a kind of dry resin secreted by the Garcinia hanburyi tree, is a natural active ingredient with various biological activities, such as anti-cancer, anti-inflammatory, antioxidant, anti-bacterial effects, etc. An increasing amount of evidence indicates that GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis. In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form micelles, nanoparticles, nanofibers, and so on. In this review, we aim to offer a summary of chemical structure and properties, anti-cancer activities, drug delivery systems and combination therapy of GA, which might provide a reference to promote the development and clinical application of GA.

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Section: Anti-cancer Mechanismsmentioning

confidence: 99%

Gambogic Acid as a Candidate for Cancer Therapy: A Review

Liu

Chen

Lin

et al. 2020

IJN

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“…It promotes cell cycle progression and cell growth in cancer. In particular, a recent study demonstrated a direct role of BRD4 in ATCs, where its silencing significantly inhibited tumor growth both in vitro and in vivo [35]. Furthermore, it has been already demonstrated in mouse models that the employment of BET inhibitors (BETi), a new class of anticancer drugs design to block the activity of BRD4 and the other BET proteins, is able to suppress ATC growth and to improve survival [36].…”

Section: Tert Promoter Mutations Are a Hallmark Of Tc Aggressivenessmentioning

confidence: 99%

Telomerase and Telomeres Biology in Thyroid Cancer

Donati

Ciarrocchi

2019

IJMS

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Telomere and telomerase regulation contributes to the onset and evolution of several tumors, including highly aggressive thyroid cancers (TCs). TCs are the most common endocrine malignancies and are generally characterized by a high rate of curability. However, a small but significant percentage develops distant metastasis or progresses into undifferentiated forms associated with bad prognosis and for which poor therapeutic options are available. Mutations in telomerase reverse transcriptase (TERT) promoter are among the most credited prognostic marker of aggressiveness in TCs. Indeed, their frequency progressively increases passing from indolent lesions to aggressive and anaplastic forms. TERT promoter mutations create binding sites for transcription factors, increasing TERT expression and telomerase activity. Furthermore, aggressiveness of TCs is associated with TERT locus amplification. These data encourage investigating telomerase regulating pathways as relevant drivers of TC development and progression to foster the identification of new therapeutics targets. Here, we summarize the current knowledge about telomere regulation and TCs, exploring both canonical and less conventional pathways. We discuss the possible role of telomere homeostasis in mediating response to cancer therapies and the possibility of using epigenetic drugs to re-evaluate the use of telomerase inhibitors. Combined treatments could be of support to currently used therapies still presenting weaknesses.

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“…The relevance of BRD proteins in thyroid cancer is known and is well described in the literature. Their blocking by specific inhibitors such as JQ1 and AZD5153 has been shown to suppress tumor growth in vitro and in vivo [ 14 , 15 , 16 ]. The human proteome encodes 61 BRD modules found in 42 different proteins [ 12 ], which can be classified into eight subfamilies based on their sequence and structure [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

GSK2801 Reverses Paclitaxel Resistance in Anaplastic Thyroid Cancer Cell Lines through MYCN Downregulation

Molteni

Baldan

Damante

et al. 2023

IJMS

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Anaplastic thyroid cancer (ATC) is a very rare, but extremely aggressive form of thyroid malignancy, responsible for the highest mortality rate registered for thyroid cancer. Treatment with taxanes (such as paclitaxel) is an important approach in counteracting ATC or slowing its progression in tumors without known genetic aberrations or those which are unresponsive to other treatments. Unfortunately, resistance often develops and, for this reason, new therapies that overcome taxane resistance are needed. In this study, effects of inhibition of several bromodomain proteins in paclitaxel-resistant ATC cell lines were investigated. GSK2801, a specific inhibitor of BAZ2A, BAZ2B and BRD9, was effective in resensitizing cells to paclitaxel. In fact, when used in combination with paclitaxel, it was able to reduce cell viability, block the ability to form colonies in an anchor-independent manner, and strongly decrease cell motility. After RNA-seq following treatment with GSK2801, we focused our attention on MYCN. Based on the hypothesis that MYCN was a major downstream player in the biological effects of GSK2801, we tested a specific inhibitor, VPC-70619, which showed effective biological effects when used in association with paclitaxel. This suggests that the functional deficiency of MYCN determines a partial resensitization of the cells examined and, ultimately, that a substantial part of the effect of GSK2801 results from inhibition of MYCN expression.

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Bromodomain‑containing proteinï¿½4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer

Cited by 5 publications

References 25 publications

Gambogic Acid as a Candidate for Cancer Therapy: A Review

Gambogic Acid as a Candidate for Cancer Therapy: A Review

Telomerase and Telomeres Biology in Thyroid Cancer

GSK2801 Reverses Paclitaxel Resistance in Anaplastic Thyroid Cancer Cell Lines through MYCN Downregulation

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