Steroid receptor coactivator-3 is a pivotal target of gambogic acid in B-cell Non-Hodgkin lymphoma and an inducer of histone H3 deacetylation

Zhao, Zichu; Zhang, Xia; Wen, Lu; Yan, Sha; Hu, Jingyu; Ruan, Jun; Zhao, Fei; Cui, Guohui; Fang, Jun; Yan, Chen

doi:10.1016/j.ejphar.2016.06.048

Cited by 13 publications

(10 citation statements)

References 51 publications

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“…Previous studies have shown SRC-3 overexpression to be pivotal in many solid tumors, but the signi cance of SRC-3 in blood cancer tumors was undetermined [8][9][10]. Recently, a study showed clinical SRC-3 overexpression in the lymph nodes of B-cell NHL patients [12]. To evaluate the in vitro antilymphoma activity of SI-10 and SI-12, four MCL lines and one murine lymphoma line were treated with either SRC-3 inhibitor SI-10 or SI-12 at concentrations ranging from 0-2 µM.…”

Section: Src-3 Inhibitors Reduce the Proliferation Of Various MCL Cel...mentioning

confidence: 99%

“…The role of SRC-3 in MCL yet to be well de ned, but previous studies show that SRC-3 is highly expressed in B-cell NHL models. Pharmacological inhibition of SRC-3 with gambogic acid reduced tumor growth of diffuse large cell b cell lymphoma (DLBCL) models in vitro and in vivo through histone deacetylation and downregulation of multiple oncoproteins such as Bcl-2, cyclin D3, Bcl-6, and c-Myc [12]. Additionally, single-cell transcriptomic data suggest that SRC-3 is most highly expressed in B cells and plasma cells, suggesting a potential undiscovered role of SRC-3 in B cell receptor signaling [13].…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma

Bijou

Liu

et al. 2023

Preprint

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Mantle cell lymphoma (MCL) is a heterogeneous disease with a poor prognosis. Despite years of research in MCL, relapse occurs in patients with current therapeutic options necessitating the development of novel therapeutic agents. Previous attempts to pharmacologically inhibit SRC-3 show effectiveness in vivo and in vitro in other B cell lymphomas, and previous studies have shown that SRC-3 is highly expressed in the lymph nodes of B cell non-Hodgkin’s lymphoma patients. This suggests that SRC-3 may play a role in the progression of B cell lymphoma and that the development of selective SRC inhibitors should be investigated. This study aimed to investigate novel SRC-3 inhibitors, SI-10 and SI-12, in mantle cell lymphoma. The cytotoxic effects of SI-10 and SI-12 were evaluated in a panel of MCL cell lines in vitro by resazurin assay. The in vivo efficacy of SI-10 was confirmed in two ibrutinib-resistant models: an immunocompetent disseminated A20 mouse model of B-cell lymphoma and a human PDX model of MCL. SI-10 treatment resulted in dose-dependent cytotoxicity in a panel of MCL cell lines in vitro. Notably, SI-10 treatment also resulted in a significant extension of survival in vivo with low toxicity in both ibrutinib-resistant murine models. We have investigated SI-10 as a novel anti-lymphoma compound via the inhibition of SRC-3 activity. These findings indicate that targeting SRC-3 should be investigated in combination with current clinical therapeutics as a novel strategy to expand the therapeutic index and to improve lymphoma outcomes.

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Section: Src-3 Inhibitors Reduce the Proliferation Of Various MCL Cel...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma

Bijou

Liu

et al. 2023

Preprint

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“…Loss of SRC-3 resulted in malignant B-cell lymphoma in mice upon aging through NF-κB activation [ 154 ]. However, a recent study showed that overexpression of SRC-3 was observed in B-cell Non-Hodgkin lymphoma specimens and cells, down-regulation of SRC-3 resulted in cell cycle arrest and apoptosis [ 155 ]. Therefore, the role of SRC-3 on cancer is still not fully understood, and the genes that drive cancer may determine the function of SRC-3 in tumorigenesis.…”

Section: Implication Of Src-3 In Cancermentioning

confidence: 99%

“…Gambogic acid (GA), a main active ingredient in gamboge, exhibits effective anti-cancer activity in multiple cancer cells. Studies have reported that GA could reduce the expression of SRC-3 and inhibit the proliferation of cancer cells [ 155 , 156 ]. Cullin3, an E3 ligase involved in SRC-3 ubiquitination [ 90 ], was up-regulated under GA treatment, which may contribute to SRC-3 degradation [ 155 ].…”

Section: Src-3 As Therapeutic Targetmentioning

confidence: 99%

SRC-3, a Steroid Receptor Coactivator: Implication in Cancer

Li¹,

Deng²,

Chen³

2021

IJMS

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Steroid receptor coactivator-3 (SRC-3), also known as amplified in breast cancer 1 (AIB1), is a member of the SRC family. SRC-3 regulates not only the transcriptional activity of nuclear receptors but also many other transcription factors. Besides the essential role of SRC-3 in physiological functions, it also acts as an oncogene to promote multiple aspects of cancer. This review updates the important progress of SRC-3 in carcinogenesis and summarizes its mode of action, which provides clues for cancer therapy.

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“…[5][6][7] Other reported targets of GA include IKKb in macrophages and proteasomes, Bcl-2 family proteins, and steroid receptor coactivator-3 (SRC-3) in cancer cells. [8][9][10][11] Although some progress has been made on the target identification to explain the anticancer activity of GA, whether or not it regulates cellular metabolic processes has not been explored.…”

mentioning

confidence: 99%

Gambogic acid suppresses the pentose phosphate pathway by covalently inhibiting 6PGD protein in cancer cells

Zhu

Zhang

et al. 2022

Chem. Commun.

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Steroid receptor coactivator-3 is a pivotal target of gambogic acid in B-cell Non-Hodgkin lymphoma and an inducer of histone H3 deacetylation

Cited by 13 publications

References 51 publications

Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma

Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma

SRC-3, a Steroid Receptor Coactivator: Implication in Cancer

Gambogic acid suppresses the pentose phosphate pathway by covalently inhibiting 6PGD protein in cancer cells

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