Co-treatment of Naringenin and Ketoprofen-RGD Suppresses Cell Proliferation via Calmodulin/PDE/cAMP/PKA Axis Pathway in Leukemia and Ovarian Cancer Cells

Noori, Shokoofe; Shokri, Bahareh; Zarghi, Afshin

doi:10.5812/ijpr-136131

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…It has been identified that SCL negatively regulates the STAT3 and AKT pathways and subsequently induces apoptosis in a variety of cancer cells (Afshari et al, 2020;Pan et al, 2020). However, previous studies have not explored the upstream mechanisms by which SCL influences these pathways.…”

Section: Scl Promotes the Sumoylation Of Vegfr2 And Retained It In Th...mentioning

confidence: 99%

Sclareol attenuates liver fibrosis through SENP1‐mediated VEGFR2 SUMOylation and inhibition of downstream STAT3 signaling

Niu

Bao

et al. 2023

Phytotherapy Research

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Liver fibrosis is a key global health care burden. Sclareol, isolated from Salvia sclarea, possesses various biological activities. Its effect on liver fibrosis remains unknown. This study was proposed to evaluate the antifibrotic activity of sclareol (SCL) and explore its underlying mechanisms. Stimulated hepatic stellate cells served as an in vitro liver fibrosis model. The expression of fibrotic markers was assessed by western blot and real‐time PCR. Two classical animal models, bile duct‐ligated rats and carbon tetrachloride‐treated mice, were utilized for the in vivo experiments. The liver function and fibrosis degree were determined by serum biochemical and histopathological analyses. VEGFR2 SUMOylation was analyzed using coimmunoprecipitation assay. Our results indicated that SCL treatment restricted the profibrotic propensity of activated HSCs. In fibrotic rodents, SCL administration alleviated hepatic injury and reduced collagen accumulation. Mechanistic studies indicated that SCL downregulated the protein level of SENP1 and enhanced VEGFR2 SUMOylation in LX‐2 cells, which affected its intracellular trafficking. Blockade of the interaction between VEGFR2 and STAT3 was observed, resulting in the suppression of downstream STAT3 phosphorylation. Our findings demonstrated that SCL has therapeutic efficacy against liver fibrosis through mediating VEGFR2 SUMOylation, suggesting that SCL may be a potential candidate compound for its treatment.

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Section: Scl Promotes the Sumoylation Of Vegfr2 And Retained It In Th...mentioning

confidence: 99%

Sclareol attenuates liver fibrosis through SENP1‐mediated VEGFR2 SUMOylation and inhibition of downstream STAT3 signaling

Niu

Bao

et al. 2023

Phytotherapy Research

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Comprehensive analysis of PDE2A: a novel biomarker for prognostic value and immunotherapeutic potential in human cancers

Yu,

Song,

Wang

et al. 2024

Braz J Med Biol Res

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Phosphodiesterase 2A (PDE2A) plays a pivotal role in modulating cyclic nucleotide metabolism. Recent studies have shown that PDE2A is associated with some tumors, but its expression profiles, prognostic significance, and immunological roles in diverse cancer types remain unclear. Utilizing advanced bioinformatics tools, we performed a comprehensive analysis of PDE2A gene expression in multiple human cancers. Our study revealed that PDE2A expression was significantly reduced in the majority of cancer types and clinicopathological stages (I to IV) compared to normal tissues. Additionally, PDE2A expression was closely related to the prognosis of cancers such as stomach adenocarcinoma (STAD), ovarian serous cystadenocarcinoma (OV), and liver hepatocellular carcinoma (LIHC). Cox regression analyses indicated that PDE2A can act as an independent prognostic factor for these cancers. The level of PDE2A DNA methylation was significantly decreased in most cancers. Genetic alterations in PDE2A predominantly manifest in the form of amplifications. Moreover, infiltrating cells and immune checkpoint genes, including PDCD1, exhibited notable correlations with PDE2A expression. Significant associations were observed between PDE2A expression and tumor mutation burden as well as microsatellite instability. Single cell sequencing revealed PDE2A's crucial role in regulating differentiation and angiogenesis of cancer cells. Functional enrichment analysis emphasized the important role of PDE2A in synaptic transmission and tumor development. Aberrant expression of PDE2A influenced the sensitivity of various antitumor and chemotherapy drugs. This research provided a comprehensive analysis of PDE2A in human cancers, highlighting its potential as both a prognostic marker and an immunotherapy target for future research.

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NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer

Coutinho,

Femino,

Gonzalez

et al. 2024

IJMS

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Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies.

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Co-treatment of Naringenin and Ketoprofen-RGD Suppresses Cell Proliferation via Calmodulin/PDE/cAMP/PKA Axis Pathway in Leukemia and Ovarian Cancer Cells

Cited by 3 publications

References 36 publications

Sclareol attenuates liver fibrosis through SENP1‐mediated VEGFR2 SUMOylation and inhibition of downstream STAT3 signaling

Sclareol attenuates liver fibrosis through SENP1‐mediated VEGFR2 SUMOylation and inhibition of downstream STAT3 signaling

Comprehensive analysis of PDE2A: a novel biomarker for prognostic value and immunotherapeutic potential in human cancers

NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer

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