STAT3 signaling in prostate cancer progression and therapy resistance: An oncogenic pathway with diverse functions

Sadrkhanloo, Mehrdokht; Paskeh, Mahshid Deldar Abad; Hashemi, Mehrdad; Raesi, Rasoul; Motahhary, Motahhar; Saghari, Sam; Sharifi, Laleh; Bokaie, Saied; Mirzaei, Sepideh; Entezari, Maliheh; Aref, Amir Reza; Salimimoghadam, Shokooh; Rashidi, Mohsen; Taheriazam, Afshin; Hushmandi, Kiavash

doi:10.1016/j.biopha.2022.114168

Cited by 20 publications

(6 citation statements)

References 229 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Silencing STAT3 expression inhibits cell growth in colorectal cancer cells through G2 phase arrest, inducing apoptosis 36 . Furthermore, the activation of STAT3 signaling increases glycolysis, leading to an increase in the growth rate of prostate cancer cells 37 . Moreover, STAT3 signaling promotes EMT in colorectal cancer, hepatocellular carcinoma, and prostate cancer [37][38][39] .…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the activation of STAT3 signaling increases glycolysis, leading to an increase in the growth rate of prostate cancer cells 37 . Moreover, STAT3 signaling promotes EMT in colorectal cancer, hepatocellular carcinoma, and prostate cancer [37][38][39] . These findings indicate that the inhibition of STAT3 might be a powerful strategy for the treatment of several cancers.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism

Yeo,

Yun,

Shin

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Oral cancer stands as a prevalent maligancy worldwide; however, its therapeutic potential is limited by undesired effects and complications. As a medicinal edible fungus, Chaga mushroom (Inonotus obliquus) exhibits anticancer effects across diverse cancers. Yet, the precise mechanisms underlying its efficacy remain unclear. We explored the detailed mechanisms underlying the anticancer action of Chaga mushroom extract in oral cancer cells (HSC-4). Following treatment with Chaga mushroom extracts, we analyzed cell viability, proliferation capacity, glycolysis, mitochondrial respiration, and apoptosis. Our findings revealed that the extract reduced cell viability and proliferation of HSC-4 cells while arresting their cell cycle via suppression of STAT3 activity. Regarding energy metabolism, Chaga mushroom extract inhibited glycolysis and mitochondrial membrane potential in HSC-4 cells, thereby triggering autophagy-mediated apoptotic cell death through activation of the p38 MAPK and NF-κB signaling pathways. Our results indicate that Chaga mushroom extract impedes oral cancer cell progression, by inhibiting cell cycle and proliferation, suppressing cancer cell energy metabolism, and promoting autophagy-mediated apoptotic cell death. These findings suggest that this extract is a promising supplementary medicine for the treatment of patients with oral cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism

Yeo,

Yun,

Shin

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Here, IPA analysis suggested that STAT3 and IL6 are possible upstream regulators for KD025-induced DEGs. Interestingly, since STAT3- and IL6-related signaling are known to be pivotally involved in the mitochondrial function [ 47 ] and glycolysis [ 48 ], KD025-induced metabolic shift to produce ATP from glycolysis to mitochondrial respiration in HTM cells ( Figure 1 ) was quite rationally understood. Furthermore, in our previous analysis of RNA sequencing of 2D and 3D cultured 3T3-L1 cells, STAT3 and IL6 were also estimated as the master upstream and causal network regulators for inducing 3D spheroid formation [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

The Specific ROCK2 Inhibitor KD025 Alleviates Glycolysis through Modulating STAT3-, CSTA- and S1PR3-Linked Signaling in Human Trabecular Meshwork Cells

Watanabe,

Sato,

Umetsu

et al. 2024

Biomedicines

View full text Add to dashboard Cite

To investigate the biological significance of Rho-associated coiled-coil-containing protein kinase (ROCK) 2 in the human trabecular meshwork (HTM), changes in both metabolic phenotype and gene expression patterns against a specific ROCK2 inhibitor KD025 were assessed in planar-cultured HTM cells. A seahorse real-time ATP rate assay revealed that administration of KD025 significantly suppressed glycolytic ATP production rate and increased mitochondrial ATP production rate in HTM cells. RNA sequencing analysis revealed that 380 down-regulated and 602 up-regulated differentially expressed genes (DEGs) were identified in HTM cells treated with KD025 compared with those that were untreated. Gene ontology analysis revealed that DEGs were more frequently related to the plasma membrane, extracellular components and integral cellular components among cellular components, and related to signaling receptor binding and activity and protein heterodimerization activity among molecular functions. Ingenuity Pathway Analysis (IPA) revealed that the detected DEGs were associated with basic cellular biological and physiological properties, including cellular movement, development, growth, proliferation, signaling and interaction, all of which are associated with cellular metabolism. Furthermore, the upstream regulator analysis and causal network analysis estimated IL-6, STAT3, CSTA and S1PR3 as possible regulators. Current findings herein indicate that ROCK2 mediates the IL-6/STAT3-, CSTA- and S1PR3-linked signaling related to basic biological activities such as glycolysis in HTM cells.

show abstract

“…Prostate cancer is considered the deadliest cancer with a poor prognosis, particularly in men worldwide [29]. STAT-3 is frequently activated in prostate cancer, promoting tumor survival, growth, angiogenesis, and metastasis [30]. Hence, STAT-3 overexpression is thought to be a crucial target for the identification of new therapeutical molecules against prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

Caffeic acid hinders the proliferation and migration through inhibition of IL-6 mediated JAK-STAT-3 signaling axis in human prostate cancer

YIN,

WANG,

et al. 2024

View full text Add to dashboard Cite

Background: Caffeic acid (CA) is considered a promising phytochemical that has inhibited numerous cancer cell proliferation. Therefore, it is gaining increasing attention due to its safe and pharmacological applications. In this study, we investigated the role of CA in inhibiting the Interleukin-6 (IL-6)/Janus kinase (JAK)/Signal transducer and activator of transcription-3 (STAT-3) mediated suppression of the proliferation signaling in human prostate cancer cells. Materials and Methods: The role of CA in proliferation and colony formation abilities was studied using 3-[4,5dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay and colony formation assays. Tumour cell death and cell cycle arrest were identified using flow cytometry techniques. CA treatment-associated protein expression of mitogen-activated protein kinase (MAPK) families, IL-6/JAK/STAT-3, proliferation, and apoptosis protein expressions in PC-3 and LNCaP cell lines were measured using Western blot investigation. Results: We have obtained that treatment with CA inhibits prostate cancer cells (PC-3 and LNCaP) proliferation and induces reactive oxygen species (ROS), cell cycle arrest, and apoptosis cell death in a concentration-dependent manner. Moreover, CA treatment alleviates the expression phosphorylated form of MAPK families, i.e., extracellular signal-regulated kinase 1 (ERK1), c-Jun N-terminal kinase (JNK), and p38 in PC-3 cells. IL-6 mediated JAK/STAT3 expressions regulate the proliferation and antiapoptosis that leads to prostate cancer metastasis and migration. Therefore, to mitigate the expression of IL-6/JAK/STAT-3 is considered an important target for the treatment of prostate cancer. In this study, we have observed that CA inhibits the expression of IL-6, JAK1, and phosphorylated STAT-3 in both PC-3 and LNCaP cells. Due to the inhibitory effect of IL-6/JAK/STAT-3, it resulted in decreased expression of cyclin-D1, cyclin-D2, and CDK1 in both PC-3 cells. In addition, CA induces apoptosis by enhancing the expression of Bax and caspase-3; and decreased expression of Bcl-2 in prostate cancer cells. Conclusions: Thus, CA might act as a therapeutical application against prostate cancer by targeting the IL-6/JAK/STAT3 signaling axis.

show abstract

STAT3 signaling in prostate cancer progression and therapy resistance: An oncogenic pathway with diverse functions

Cited by 20 publications

References 229 publications

Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism

Chaga mushroom extract suppresses oral cancer cell growth via inhibition of energy metabolism

The Specific ROCK2 Inhibitor KD025 Alleviates Glycolysis through Modulating STAT3-, CSTA- and S1PR3-Linked Signaling in Human Trabecular Meshwork Cells

Caffeic acid hinders the proliferation and migration through inhibition of IL-6 mediated JAK-STAT-3 signaling axis in human prostate cancer

Contact Info

Product

Resources

About