Bromodomain and extra-terminal inhibitors emerge as potential therapeutic avenues for gastrointestinal cancers

Sun, Huiyan; Du, Songtao; Li, Yayun; Deng, Guangtong; Zeng, Furong

doi:10.4251/wjgo.v14.i1.75

Cited by 13 publications

(18 citation statements)

References 100 publications

(100 reference statements)

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“…Indeed, numerous studies have reported that the upregulation of BETs leads to abnormal transcriptional regulation which facilitates tumor initiation and progression 155 . Consistently, the downregulation of BETs expression and inactivation of their function represent a potential mechanism for the antitumor effects of BETs inhibitors 156 . Moreover, BET inhibition exhibits outstanding antiinflammatory properties in several pathophysiological conditions 157,158 …”

Section: New Regulatory Pathways Of Cholesterol Metabolismmentioning

confidence: 97%

Regulation of cholesterol metabolism: New players for an old physiological process

Parente,

Tonini,

Segatto

et al. 2023

J of Cellular Biochemistry

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Identified more than two centuries ago, cholesterol plays a pivotal role in human physiology. Since cholesterol metabolism is a physiologically significant process, it is not surprising that its alterations are associated with several pathologies. The discovery of new molecular targets or compounds able to modulate this sophisticated metabolism has been capturing the attention of research groups worldwide since many years. Endogenous and exogenous compounds are known to regulate cellular cholesterol synthesis and uptake, or reduce cholesterol absorption at the intestinal level, thereby regulating cholesterol homeostasis. However, there is a great need of new modulators and diverse new pathways have been uncovered. Here, after illustrating cholesterol metabolism and its well‐known regulators, some new players of this important physiological process are also described.

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Section: New Regulatory Pathways Of Cholesterol Metabolismmentioning

confidence: 97%

Regulation of cholesterol metabolism: New players for an old physiological process

Parente,

Tonini,

Segatto

et al. 2023

J of Cellular Biochemistry

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“…BET inhibitors function primarily by competitively binding to BET proteins and disrupting the interaction between BET proteins and acetylated lysine residues 32 . To determine which BET proteins are responsible for IL6/STAT3 pathway signaling, we silenced BRD2/3/4 individually using shRNA (Fig.…”

Section: Apoptosis and Cell Cycle Arrest Mediate The Synergy Induced ...mentioning

confidence: 99%

BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression

Zeng

et al. 2023

Exp Mol Med

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Targeting bromodomain and extra-terminal domain (BET) proteins has shown a promising therapeutic effect on melanoma. The development of strategies to better kill melanoma cells with BET inhibitor treatment may provide new clinical applications. Here, we used a drug synergy screening approach to combine JQ1 with 240 antitumor drugs from the Food and Drug Administration (FDA)-approved drug library and found that sunitinib synergizes with BET inhibitors in melanoma cells. We further demonstrated that BET inhibitors synergize with sunitinib in melanoma by inducing apoptosis and cell cycle arrest. Mechanistically, BET inhibitors sensitize melanoma cells to sunitinib by inhibiting GDF15 expression. Strikingly, GDF15 is transcriptionally regulated directly by BRD4 or indirectly by the BRD4/IL6/STAT3 axis. Xenograft assays revealed that the combination of BET inhibitors with sunitinib causes melanoma suppression in vivo. Altogether, these findings suggest that BET inhibitor-mediated GDF15 inhibition plays a critical role in enhancing sunitinib sensitivity in melanoma, indicating that BET inhibitors synergize with sunitinib in melanoma.

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“…[25] Overexpression of these proteins was associated with several cancers such as colorectal, pancreatic, gastric, prostate and breast cancers. [27][28][29][30][31] Due to their oncogenic behavior, BRD inhibitors have been developed and investigated by multiple researchers. [27,32] Data in literature suggest that BRD inhibition yields successful outcomes in cancer treatment.…”

Section: Biological Activitymentioning

confidence: 99%

New Flavone Derivatives Targeting BET Proteins in Cancer: Synthesis, Structure Analysis and Investigation of Bromodomain Inhibitory Activities**

Gultekin,

Ozkan,

Bakar‐Ates

et al. 2023

ChemistrySelect

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Bromodomains (BRDs) are key transcriptional regulators that control expression of genes. Dysfunction of BRDs has been associated with the development of aggressive tumors. BRDs have emerged as attractive candidates for the development of inhibitors targeting gene transcription. Flavones can act as a potent anticancer agent. In this paper, a series of ten new flavonylquinazoline sulfonamide compounds (FQ1‐FQ10) was synthesized and their cytotoxicity was investigated in human A549 lung carcinoma, MCF‐7 breast carcinoma ve K562 myeloid leukemia cell lines. The most cytotoxic compounds FQ1 and FQ6 were tested for their bromodomain containing 2 protein (BRD2), bromodomain containing 3 protein (BRD3) and bromodomain containing 4 protein (BRD4) inhibitor activities. The results showed that new FQ1 and FQ6 flavone compounds exhibited BRD2, BRD3 inhibitor activity. We suggest that flavonylquinazoline sulfonamide compounds have the potential to inhibit bromodomain activity, thus may be pharmacologically of interest for further investigations.

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Bromodomain and extra-terminal inhibitors emerge as potential therapeutic avenues for gastrointestinal cancers

Cited by 13 publications

References 100 publications

Regulation of cholesterol metabolism: New players for an old physiological process

Regulation of cholesterol metabolism: New players for an old physiological process

BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression

New Flavone Derivatives Targeting BET Proteins in Cancer: Synthesis, Structure Analysis and Investigation of Bromodomain Inhibitory Activities**

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