PRKCA (Protein Kinase C Alpha)

Six compounds were isolated from H. giganteus, with 4 exhibiting antiproliferative activity through PRKCA and GSK3β modulation. These findings provide the first phytochemical and mechanistic evidence that support H. giganteus as a promising source of active anti-colon cancer leads.

This process attenuates p38 MAPK phosphorylation, which in turn drives BC progression. Together, our work defines a key signaling axis-DTX3L-PKCα-p38 MAPK-in BC progression and provide important insights for the diagnosis and treatment of this disease.

FTA treatment promoted Beclin-1 and LC3B II/LC3B I expressions, and inhibited PKCα and p-p65/p65 expressions in prostate tissues of CNP rat models. FTA alleviates inflammation and facilitates autophagy in CNP rat models by blocking the PKCα/NF-κB pathway.

The overexpression of ATP synthase-related proteins ATP5A1 and ATP5C1 in the tumor microenvironment of MDA-MB-231 xenograft mice were also significantly suppressed by DET and DETD-35 treatments. In summary, this study identifies DETD-35 and DET as novel ATPase inhibitors which are attributed to disrupting mitochondrial biogenetics and cellular metabolism and networking in TNBC cells.

In vitro 2D cytotoxicity assays demonstrated potent antiproliferative activity, with IC₅₀ values of 3.93 ± 0.47 μM in A549 and 4.88 ± 1.42 μM in non-small cell lung cancer (NSCLC) cells, while showing reduced cytotoxicity in normal fibroblasts (MRC-5; IC₅₀ = 10.48 ± 1.83 μM) compared with osimertinib. Molecular docking and in silico conformational analyses demonstrated strong binding affinity of compound 3 to the VEGFR-2 kinase domain, stabilizing critical active-site residues and supporting a structure-based mechanism of action. Collectively, these findings validate VEGFR-2 as a therapeutic target and highlight compound 3 as a promising scaffold for structure-based drug development against non-small cell lung cancer.

Gastric cancer (GC) is often associated with high invasiveness, epithelial-mesenchymal transition (EMT), and resistance to 5-fluorouracil (5-FU), highlighting the need for novel therapeutic targets...DADS inhibits GC progression and enhances 5-FU sensitivity by PKCα/RORα-mediated downregulation of RORα/β-catenin signaling, paralleling SR1078/TPA effects. It may act as a novel RORα agonist for GC therapy.

Current chemotherapy treatments, including the TIP (Taxol, Ifosfamide, Cisplatin) regimen, have shown limited effects but strong side effects in advanced Penile squamous cell carcinoma (PSCC) patients. Furthermore, compared with cisplatin, TROP-2 targeted ADC could achieve an equivalent inhibitory effect on the proliferation of PSCC both in vivo and in vitro. TROP-2 promoted PSCC cell proliferation via AKT/PKCα-dependent pathway, and TROP-2-targeted ADC-drug has a gratifying inhibitory effect on PSCC proliferation both in vivo and in vitro.

Unexpectedly, increased editing levels in select genes ( CD247 , PRKCA and TRAF3IP2.ASI in T-ALL; SPPL3 in B-ALL) were significantly associated with better patient survival, suggesting a potential prognostic role for editing dysregulation at individual gene levels. Together, these results deepen our understanding of the pediatric ALL transcriptome landscape and provided novel candidate regulators and therapeutic targets for future mechanistic and translational investigation.

Bioinformatic analysis of mEGFR lung cancers highlighted basal cells, a subtype of lung cell which intrinsically express high PRKCA, as the likely cell-of-origin, suggesting that cell lineage sets a high ceiling for PKCα abundance, while mEGFR licenses the activation of the kinase. Collectively, these data define a pathway-specific role for cPKCs, particularly PKCα, as upstream effectors of mTORC1 in mEGFR systems, establishing a neomorphic dependency on the PKCα-AKT-mTORC1 signaling arm that sustains tumorigenesis via biased signaling by the mutant receptor.

D463H expression reduced the sensitivity of cells to the BET inhibitors JQ1 and AZD5153, indicating the functional importance of these pathways. The findings indicate that D463H is a dominant gain-of-function oncogenic mutant that operates through a noncatalytic allosteric mechanism.

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