Discovery of a chalcone derivative as an anti-fibrotic agent targeting transforming growth factor-β1 signaling: Potential therapy of renal fibrosis

Poolsri, Wanangkan; Noitem, Rattikarn; Jutabha, Promsuk; Raveesunthornkiat, Manasanan; Danova, Ade; Chavasiri, Warinthorn; Muanprasat, Chatchai

doi:10.1016/j.biopha.2023.115098

Cited by 3 publications

(1 citation statement)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TGFβ is one of the main inducing factors for tumor matrix formation, playing important roles in carcinoma-associated fibroblast activation, tumor microenvironment construction, immune escape, and drug resistance ( 12 , 17 , 18 ). It also promotes the occurrence and development of fibrotic diseases ( 19 , 20 ). Pancreatic adenocarcinoma tumors are dense solid tumors with significantly enhanced stromal connective tissue response, characterized by a high degree of fibrosis in the ECM ( 21 – 23 ).…”

Section: Introductionmentioning

confidence: 99%

PET imaging with [68Ga]-labeled TGFβ-targeting peptide in a mouse PANC-1 tumor model

Li,

Zhao,

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

PurposeTransforming growth factor β (TGFβ) is upregulated in many types of tumors and plays important roles in tumor microenvironment construction, immune escape, invasion, and metastasis. The therapeutic effect of antibodies and nuclide-conjugated drugs targeting TGFβ has not been ideal. Targeting TGFβ with small-molecule or peptide carriers labeled with diagnostic/therapeutic nuclides is a new development direction. This study aimed to explore and confirm the imaging diagnostic efficiency of TGFβ-targeting peptide P144 coupled with [68Ga] in a PANC-1 tumor model.ProceduresTGFβ-targeting inhibitory peptide P144 with stable activity was prepared through peptide synthesis and screening, and P144 was coupled with biological chelator DOTA and labeled with radionuclide [68Ga] to achieve a stable TGFβ-targeting tracer [68Ga]Ga-P144. This tracer was first used for positron emission tomography (PET) molecular imaging study of pancreatic cancer in a mouse PANC-1 tumor model.Results[68Ga]Ga-P144 had a high targeted uptake and relatively long uptake retention time in tumors and lower uptakes in non-target organs and backgrounds. Target pre-blocking experiment with the cold drug P144-DOTA demonstrated that the radioactive uptake with [68Ga]Ga-P144 PET in vivo, especially in tumor tissue, had a high TGFβ-targeting specificity. [68Ga]Ga-P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect.Conclusion[68Ga]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGFβ-positive malignancies.

show abstract

Section: Introductionmentioning

confidence: 99%

PET imaging with [68Ga]-labeled TGFβ-targeting peptide in a mouse PANC-1 tumor model

Li,

Zhao,

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

show abstract

Factors Affecting the Evaluation of Collagen Deposition and Fibrosis In Vitro

Fathi,

Sundaresan,

Alfonso

et al. 2024

Tissue Engineering Part A

View full text Add to dashboard Cite

Discovery of Loureirin analogues with colorectal cancer suppressive activity via regulating cell cycle and Fas death receptor

Li,

Tian,

Zhang

et al. 2024

BMC Pharmacol Toxicol

View full text Add to dashboard Cite

Chalcones and dihydrochalcones (DHCs) are important bioactive natural products (BNPs) isolated from traditional Chinese medicine. In this study, 13 chalcones were designed with the inspiration of Loureirin, a DHC extracted from Resina Draconis, and synthesized by classical Claisen-Schmidt reactions. Afterwards the reduction reactions were carried out to obtain the corresponding DHCs. Cytotoxicity assay indicated chalcones and DHCs possessed selective cytotoxicity against colorectal cancer (CRC) cells. The preliminary structure-activity relationships (SAR) of these compounds suggested the α, β-unsaturated ketone of the chalcones were crucial for the anticancer activity. Interestingly, compounds 3d and 4c exhibited selective anticancer activity against CRC cell line HCT116 with IC50s of 8.4 and 17.9 μM but not normal cell. Moreover, 4c could also inhibit the migration and invasion of CRC cells. Mechanism investigations showed 4c could induce cell cycle G2/M arrest by regulating cell cycle-associated proteins and could also up-regulate Fas cell surface death receptor. The virtual docking further pointed out that compounds 3d and 4c could nicely bind to the Fas/FADD death domain complex (ID: 3EZQ). Furthermore, silencing of Fas significantly enhanced the proliferation of CRC cells and attenuated the cytotoxicity induced by 4c. These results suggested 4c exerted its anticancer activity possibly regulating cell cycle and Fas death receptor. In summary, this study investigated the anticancer activity and mechanism of Loureirin analogues in CRC, suggesting these compounds may warrant further investigation as promising anticancer drug candidates for the treatment of CRC.

show abstract

Discovery of a chalcone derivative as an anti-fibrotic agent targeting transforming growth factor-β1 signaling: Potential therapy of renal fibrosis

Cited by 3 publications

References 39 publications

PET imaging with [68Ga]-labeled TGFβ-targeting peptide in a mouse PANC-1 tumor model

PET imaging with [68Ga]-labeled TGFβ-targeting peptide in a mouse PANC-1 tumor model

Factors Affecting the Evaluation of Collagen Deposition and Fibrosis In Vitro

Discovery of Loureirin analogues with colorectal cancer suppressive activity via regulating cell cycle and Fas death receptor

Contact Info

Product

Resources

About