Discovery of imidazopyridine-pyrazoline-hybrid structure as SHP-1 agonist that suppresses phospho-STAT3 signaling in human breast cancer cells

Yang, Min Hee and Sethi, Gautam and Ravish, Akshay and Mohan, Arun Kumar and Pandey, Vijay and Lobie, Peter E. and Basappa, Shreeja and Basappa, Basappa and Ahn, Kwang Seok (2023) Discovery of imidazopyridine-pyrazoline-hybrid structure as SHP-1 agonist that suppresses phospho-STAT3 signaling in human breast cancer cells. Chemico-Biological Interactions, 386. ISSN 00092797

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Abstract

Signal transducer and activator of transcription 3 (STAT3) promotes breast cancer malignancy and controls key processes including proliferation, differentiation, and survival in breast cancer cells. Although many methods for treating breast cancer have been improved, there is still a need to discover and develop new methods for breast cancer treatment. Therefore, we synthesized a new compound 2-(4-(2,3-dichlorophenyl)piperazin-1-yl)-1-(3-(2,6-dimethylimidazo1,2-apyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (DIP). We aimed to evaluate the anti-cancer effect of DIP in breast cancer cells and clarify its mode of action. We noted that DIP abrogated STAT3 activation and STAT3 upstream kinases janus-activated kinase (JAK) and Src kinases. In addition, DIP promoted the levels of SHP-1 protein and acts as SHP-1 agonist. Further, silencing of SHP-1 gene reversed the DIP-induced attenuation of STAT3 activation and apoptosis. DIP also induced apoptosis through modulating PARP cleavage and oncogenic proteins. Moreover, DIP also significantly enhanced the apoptotic effects of docetaxel through the suppression of STAT3 activation in breast cancer cells. Overall, our data indicated that DIP may act as a suppressor of STAT3 cascade, and it could be a new therapeutic strategy in breast cancer cells. © 2023 Elsevier B.V.

Item Type:	Article
Additional Information:	Cited by: 3
Uncontrolled Keywords:	Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Humans; Phosphorylation; STAT3 Transcription Factor; 2 4 (2,3 dichlorophenyl)piperazin 1 yl 1 3 (2,6 dimethylimidazo1,2 a]pyridin 3 yl) 5 (3 nitrophenyl) 4,5 dihydro 1h pyrazol 1 yl]ethanone; docetaxel; imidazopyridine derivative; Janus kinase; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein tyrosine kinase; pyrazoline derivative; STAT3 protein; unclassified drug; antineoplastic agent; imidazopyridine derivative; PTPN6 protein, human; STAT3 protein; STAT3 protein, human; antineoplastic activity; apoptosis; Article; breast cancer; cancer cell; controlled study; drug mechanism; drug screening; drug structure; drug synthesis; gene silencing; human; human cell; protein cleavage; protein phosphorylation; signal transduction; breast tumor; cell proliferation; female; metabolism; phosphorylation; tumor cell line
Subjects:	C Chemical Science > Organic Chemistry
Divisions:	Department of > Organic Chemistry
Depositing User:	Mr Umendra uom
Date Deposited:	01 Dec 2025 07:13
Last Modified:	01 Dec 2025 07:13
URI:	http://eprints.uni-mysore.ac.in/id/eprint/18128

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