GADD45A (Growth arrest and DNA-damage-inducible, alpha)

Notably, SC downregulated the mechanosensitive ion channel PIEZO1, and its inhibitor ruthenium red (RR) significantly reversed SC-induced proliferation inhibition and G2/M arrest. This study delineates an antitumor mechanism of SC mediated via a calcium-ER stress-cell cycle axis with translational potential for non-small cell lung cancer (NSCLC) cells therapy.

The GSK-3ß inhibitor and Actinonin combination demonstrated a powerful tumor-suppressive effect in vivo without severe side effects. Combining GSK-3ß inhibition with Actinonin can effectively eliminate cancer cells with HNF-1ß overexpression by inhibiting glycolysis and promoting mitochondrial turnover, highlighting new options for cancer therapy.

In summary, the GADD45 family serves as a crucial link between stress signaling, genomic stability, and immune regulation. Gaining a clearer understanding of their isoform-specific and context-dependent functions will be vital to fully leverage their potential as biomarkers and therapeutic targets in precision oncology.

It is concluded that UA exhibits antiproliferative actions, promoting changes in the expression of genes associated with cell cycle control and DNA damage. This study has contributed to understanding the mechanism of action of this phytochemical for its therapeutic potential.

Proliferation inhibition caused by PKR knockdown was reversed by downregulation of GADD45A, suggesting that PKR and GADD45A interact to regulate PDAC cell growth. PKR promotes PDAC cell proliferation by modulating the cell cycle via regulation of GADD45A expression, demonstrating its potential as a therapeutic target for PDAC.

Finally, we discuss translational strategies to harness GADD45α activity, ranging from small-molecule enhancers and epigenetic modifiers to precision gene-editing to reinforce DNA repair capacity, delay senescence onset, and extend organismal healthspan. This review reframes GADD45α from a cancer-centric effector to a versatile regulator of aging processes, underscoring its therapeutic potential for promoting healthy longevity.

Moreover, when AML cell lines were treated with a DNA methylation inhibitor, TPTEP1 expression was up-regulated. This study reveals that the lncRNA TPTEP1 regulates the expression of GADD45α by sponging miR-4295 in AML cells, which may represent a novel therapeutic target for AML.

A decrease in MI at 100 µg/mL was observed. These findings indicate that pioglitazone does not exhibit genotoxic effects under hyperglycemic conditions.

Co-treatment of CTCL with subtoxic doses of curcumin and bortezomib potentiated the anticancer action. Co-treatment of CTCL with subtoxic doses of curcumin and bortezomib potentiated the anticancer action. Molecular docking studies revealed a strong binding affinity of curcumin to the active site of SKP2, primarily involving key residues crucial for its activity. Altogether, our results suggest that targeting SKP2 and GADD45A signaling by curcumin could be an attractive strategy for the treatment of CTCL.

Additionally, qRT-PCR assessed key molecules in apoptosis, cell cycle regulation, and DNA damage response, including GADD45α, PARP1, p38α, p53, FoxO3a, and RbL2. Our findings suggest that DT inhibits HT-29 cell proliferation, induces apoptosis, and impacts DNA damage response, highlighting its potential as a therapeutic agent requiring further investigations.

In addition, carfilzomib inhibited Huh7 cell growth in vivo. To conclude, the present research revealed that carfilzomib inhibits the progression of HCC cells by upregulating GADD45α expression, suggesting that carfilzomib could be a potential chemotherapeutic agent against HCC.

Elucidation of these pathways in cervical cancer may ultimately lead to novel and more effective treatments. Here, we highlight apoptosis-inducing drug as a therapeutic strategy to regulate the process of carcinogenesis, and regulating apoptosis could benefit cancer treatment and prevention.