Targeting JAK2/STAT3 for the treatment of cancer: A review on recent advancements in molecular development using structural analysis and SAR investigations

Kohal, Rupali; Bisht, Priya; Gupta, Ghanshyam Das; Verma, Sant Kumar

doi:10.1016/j.bioorg.2023.107095

Cited by 10 publications

(1 citation statement)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, the JAK2/ STAT3 pathway has attracted attention as a potential target for creating new anti-tumor drugs. It shows promise in treating various types of solid cancers [8]. Many studies have demonstrated that numerous bioactive compounds from natural plants or Chinese medicine have shown antitumor properties against multiple cancers by inhibiting the JAK2/STAT3 pathway in vivo and in intro [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway

CHEN,

WU,

WANG

et al. 2024

BIOCELL

View full text Add to dashboard Cite

Background: Oleanolic acid (OA), a pentacyclic triterpenoid exhibiting specific anti-cancer properties and highly effective antioxidant activity, was isolated from traditional Chinese medicinal herbs. Conversely, the OA that impacts colon cancer (CC) cells and its underlying mechanisms remain poorly understood. Methods: The cytotoxic effect of OA alone or OA-5-Fluorouracil (5-FU) combination on normal and CC cells was analyzed by methyl thiazolyl diphenyl-tetrazolium bromide (MTT). Then, the impact of OA on CC cell lines (LoVo and HT-29) proliferation and stemness were measured using colon formation and tumorsphere formation assays. Octamerbinding transcription factor 4 (Oct4), Prominin-1 (CD133), Nanog, and transcription factor SOX-2 (SOX2) are cell stemness-related indicators whose expression was assessed using fluorescence qPCR assay, Western blotting, and immunohistochemistry. The effect of OA on the proliferative potency of CC cells was evaluated using an in vivo model. Results: The stem-like characteristics and clone production of colon cancer cells were markedly reduced by OA alone or in combination with OA-5-FU. Moreover, OA increases the susceptibility of CC cells to 5-FU by blocking the cell stemness-related markers (CD133, Nanog, SOX2, and Oct4) expression levels both in vitro and in vivo, as well as by inactivating the activator of transcription 3 (STAT3 signaling) and Janus kinase 2/signal transducer (JAK2). Conclusion: These findings imply that oleanolic acid, both in vitro and in vivo, suppresses the JAK2/STAT3 pathway, which in turn reverses chemoresistance and decreases colon cancer cell stemness. Therefore, by reducing the recommended amount of 5-FU, this strategy may improve chemotherapeutic effectiveness and minimize undesired side effects.

show abstract

Section: Introductionmentioning

confidence: 99%

Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway

CHEN,

WU,

WANG

et al. 2024

BIOCELL

View full text Add to dashboard Cite

show abstract

Unraveling the Pathogenesis of Post‐Stroke Depression in a Hemorrhagic Mouse Model through Frontal Lobe Circuitry and JAK‐STAT Signaling

Wu,

Deng,

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Post‐stroke depression is a common complication that imposes significant burdens and challenges on patients. The occurrence of depression is often associated with frontal lobe hemorrhage, however, current understanding of the underlying mechanisms remains limited. Here, the pathogenic mechanisms associated with the circuitry connectivity, electrophysiological alterations, and molecular characteristics are investigated related to the frontal lobe in adult male mice following unilateral injection of blood in the medial prefrontal cortex (mPFC). It is demonstrated that depression is a specific neurological complication in the unilateral hematoma model of the mPFC, and the ventral tegmental area (VTA) shows a higher percentage of connectivity disruption compared to the lateral habenula (LHb) and striatum (STR). Additionally, long‐range projections originating from the frontal lobe demonstrate higher damage percentages within the connections between each region and the mPFC. mPFC neurons reveal reduced neuronal excitability and altered synaptic communication. Furthermore, transcriptomic analysis identifies the involvement of the Janus Kinase‐Signal Transducer and Activator of Transcription (JAK‐STAT) signaling pathway, and targeting the JAK‐STAT pathway significantly alleviates the severity of depressive symptoms. These findings improve the understanding of post‐hemorrhagic depression and may guide the development of efficient treatments.

show abstract

LMOD1 Exerts a Tumor‐Suppressive Role in Breast Cancer by Restraining the JAK2/STAT3 Pathway

Fang,

Wen,

Hou

et al. 2024

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Breast cancer has seriously affected women's physical and mental health. This investigation aims at screening differentially expressed genes (DEGs) in breast cancer and illuminating the potential biological functions of Leiomodin 1 (LMOD1) and its behind mechanisms against breast cancer. The common DEGs (co‐DEGs) between the GSE22820 and GSE29431 data sets and pivotal genes were screened out using bioinformatics methods. The biological roles of LMOD1 overexpression on malignant phenotypes were validated by functional assays and the impact on fatty acid synthesis was also elucidated in breast cancer cell lines. Additionally, colivelin, a STAT3 activator, was applied for further investigating the role of LMOD1 on the JAK2/STAT3 pathway in vitro. A total of 208 co‐DEGs and 5 focal genes were screened through bioinformatics analysis, and 5 focal genes were downregulated in breast cancer cell lines. LMOD1 overexpression retarded proliferative, migratory, invasive capabilities of breast cancer cells. LMOD1 overexpression suppressed fatty acid synthesis. Furthermore, the inhibitory effects on malignant phenotypes of breast cancer cells with LMOD1 overexpression were partially abolished after colivelin treatment. Additionally, LMOD1 could impede fatty acid synthesis in breast cancer cells. Our study highlighted LMOD1 exerted as a tumor‐suppressive role in breast cancer, which was correlated with restraining the JAK2/STAT3 pathway activation.

show abstract

Targeting JAK2/STAT3 for the treatment of cancer: A review on recent advancements in molecular development using structural analysis and SAR investigations

Cited by 10 publications

References 119 publications

Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway

Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway

Unraveling the Pathogenesis of Post‐Stroke Depression in a Hemorrhagic Mouse Model through Frontal Lobe Circuitry and JAK‐STAT Signaling

LMOD1 Exerts a Tumor‐Suppressive Role in Breast Cancer by Restraining the JAK2/STAT3 Pathway

Contact Info

Product

Resources

About