C644‐0303, a small‐molecule inhibitor of the Wnt/β‐catenin pathway, suppresses colorectal cancer growth

Yan, Yu; Zhang, Yidan; Li, Mengyuan; Zhang, Yazhou; Zhang, Xinxin; Zhang, Xiaonan; Xu, Yuting; Wei, Wei; Wang, Jie; Xu, Xiaohan; Song, Qiaoling; Zhao, Chenyang

doi:10.1111/cas.15118

Cited by 5 publications

(3 citation statements)

References 76 publications

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“… 25 Inhibition of Wnt/β-catenin pathway through C644-0303 also impedes the growth of colorectal cancer. 26 In the current study, the expression levels of β-catenin, c-myc and MMP-7 were notably diminished in both AGS and MKN45 cells with transfection of shRAD54B and notably increased in both AGS and MKN45 cells transfected with RAD54B over-expression plasmid, which also confirmed in vivo . However, the contrary results were obtained in the relative protein expression of Axin in both AGS and MKN45 cells.…”

Section: Discussionsupporting

confidence: 81%

RAD54B promotes gastric cancer cell migration and angiogenesis via the Wnt/β-catenin pathway

Li,

Geng,

et al. 2024

Radiology and Oncology

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Background Gastric cancer is an epidemic malignancy that is commonly diagnosed at the late stage. Evidence has elucidated that RAD54B exerts a crucial role in the progress of various tumors, but its specific role and mechanism in gastric cancer remain gloomy. Materials and methods The level of RAD54B was detected by western blot. RAD54B expression was downregulated or upregulated in both MKN45 and AGS cells by the transfection of shRAD54B or overexpression plasmid, respectively. The role of RAD54B in the growth, migration, invasion and tube formation of gastric cancer was evaluated by Edu, colony formation, transwell and tube formation assays. In addition, the molecular mechanism of RAD54B in gastric cancer was also determined by western blot. Moreover, in vivo experiment was conducted in xenografted mice. Results The expression of RAD54B was discovered to be upregulated in gastric cancer based on the ATGC and GEPIA databases, which was also confirmed in gastric cancer cell lines. Moreover, overexpression of RAD54B enhanced the growth, migration, invasion, tube formation and Wnt/β-catenin signaling axis in AGS and MKN45 cells. As expected, knockdown of RAD54B in AGS and MKN45 cells reversed these promotions. More importantly, in vivo assay also verified that RAD54B accelerated the growth of gastric cancer and Wnt/β-catenin signaling pathway. Conclusions Both loss-of-function and gain-of-function assays demonstrated that RAD54B facilitated gastric cancer cell progress and angiogenesis through the Wnt/β-catenin axis.

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Section: Discussionsupporting

confidence: 81%

RAD54B promotes gastric cancer cell migration and angiogenesis via the Wnt/β-catenin pathway

Li,

Geng,

et al. 2024

Radiology and Oncology

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“…Because HCT116 cells have detectable levels of HIF and WNT under a steady state and also respond to additional stimulus treatment, this allows us to study all interested characteristics in the same cell under both resting and stimulatory states. Although no anticancer HIF and WNT inhibitors are clinically available, some small-molecule inhibitors specific for HIF ( 46 ) or WNT ( 47 ) signaling exhibit sound HCT116 cell growth inhibition activity. Therefore, HIF1α and WNT luciferase reporter systems were developed in the HCT116 cells through multiple steps, which resulted in generating constructs that consisted of the luciferase reporter gene under the transcriptional regulation of an enhancer containing hypoxia-responsive element (HRE) or β-catenin–binding cis element (TCF/LEF1) upstream of a mini-TATA promoter, respectively.…”

Section: Resultsmentioning

confidence: 99%

Visible light–initiated radical 1,3-difunctionalization of β,γ-unsaturated ketones

et al. 2022

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Radical-mediated 1,2-difunctionalization of olefins is a well-established synthetic technique widely used in the rapid construction of structurally diverse molecular entities. However, radical-mediated 1,3-difunctionalization reactions are rare, and the substrates are generally limited to strained skeletons. Here, we report a practical approach for 1,3-difunctionalization of available β,γ-unsaturated ketones via a radical cascade process including visible light–irradiated radical addition, thermodynamic stability–driven 1,2-carbonyl migration from unactivated all-carbon quaternary center, and terminal C-radical varied transformations. Various highly functionalized alkyl skeletons with different valuable functional groups at positions 1 and 3 and the carbonyl group at position 2 have been synthesized through a radical chain pathway or Cu-catalyzed Ritter-type reaction. Moreover, this protocol provides a real case of diversity-oriented radical rearrangement for drug discovery. We identified a previously unknown chemotype of dual inhibitors for hypoxia-inducible factor (HIF) and WNT signaling pathways from products. These small-molecule inhibitors could suppress HIF and WNT signaling–dependent HCT116 cell growth in 2D and 3D culture systems.

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“…Moreover, it has been suggested that shikonin-induced glycolysis (including the reduction of glucose 6-phosphate and pyruvate and the down-regulation of HK2 and PKM2) can be affected by RIP1 or RIP3 ( 186 ). PFKFB3 inhibitors can regulate the interaction of RIP1, RIP3 and MLKL, and induce necrotic apoptosis ( 187 ). There is a similar process of glycolysis during osteoarthritis as described above, and therefore intervention in necroptosis can rely on glycolytic interference.…”

Section: The Regulated Programmed Cell Death and Glycolysismentioning

confidence: 99%

Glycolysis: an emerging regulator of osteoarthritis

Jiang,

Guo,

Liu

et al. 2024

Front. Immunol.

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Osteoarthritis (OA) has been a leading cause of disability in the elderly and there remains a lack of effective therapeutic approaches as the mechanisms of pathogenesis and progression have yet to be elucidated. As OA progresses, cellular metabolic profiles and energy production are altered, and emerging metabolic reprogramming highlights the importance of specific metabolic pathways in disease progression. As a crucial part of glucose metabolism, glycolysis bridges metabolic and inflammatory dysfunctions. Moreover, the glycolytic pathway is involved in different areas of metabolism and inflammation, and is associated with a variety of transcription factors. To date, it has not been fully elucidated whether the changes in the glycolytic pathway and its associated key enzymes are associated with the onset or progression of OA. This review summarizes the important role of glycolysis in mediating cellular metabolic reprogramming in OA and its role in inducing tissue inflammation and injury, with the aim of providing further insights into its pathological functions and proposing new targets for the treatment of OA.

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C644‐0303, a small‐molecule inhibitor of the Wnt/β‐catenin pathway, suppresses colorectal cancer growth

Cited by 5 publications

References 76 publications

RAD54B promotes gastric cancer cell migration and angiogenesis via the Wnt/β-catenin pathway

RAD54B promotes gastric cancer cell migration and angiogenesis via the Wnt/β-catenin pathway

Visible light–initiated radical 1,3-difunctionalization of β,γ-unsaturated ketones

Glycolysis: an emerging regulator of osteoarthritis

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