A novel 1,8-naphthalimide-piperazine-amidobenzenesulfonamide derivative targets carbonic anhydrase IX to induce ferroptosis, apoptosis and autophagy in colorectal cancer cells.

Carbonic anhydrases (CAs) are crucial for cancer cells to survive in hypoxia. Here we show that our newly synthesised 1,8-naphthalimide-piperazine-amidobenzenesulfonamide derivative, namely compound Q, specifically targets CA IX and causes cell death in colorectal cancer. Compound Q stably binds to the zinc atom in the active pocket of CA IX and selectively inhibits the activity of this enzyme.

Functionalized chitosan as nano-delivery platform for CRISPR-Cas9 in cancer treatment.

CRISPR-Cas system permanently deletes any harmful gene-of-interest to combat cancer growth. Chitosan (CS) is a potential cancer therapeutic that mediates via PI3K/Akt/mTOR, MAPK and NF-kβ signaling pathway modulation. CS and its covalent derivatives have been designed as nanocarrier of CRISPR-Cas9 alone (plasmid or ribonucleoprotein) or in combination with chemical drug for cancer treatment.

Discovery of novel 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives as potent carbonic anhydrase IX inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer.

A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX.

The potential of carbonic anhydrase enzymes as a novel target for anti-cancer treatment.

Carbonic anhydrase (CA) is a zinc-dependent metal enzyme that maintains the pH and carbon dioxide (CO) homeostasis in cells by catalyzing the reversible hydration and dehydration of CO and bicarbonate (HCO). In mammals, there are 16 isozymes of CA existed, namely CAI to CAXIV, but only 15 isozymes are found in humans except CAXV. Human CAs have highly conserved catalytic domains, all of which are distributed in different tissues and play important physiological roles.

Increased RUNX1 mutations in breast cancer disease progression.

Despite advances in screening, therapy and surveillance, breast cancer remains threatening to women. Worst, patients suffer from side effects of treatments and cancer cells become resistant. The emergence of RUNX1 in breast cancer has put it in a spotlight due to its roles in the disease progression.

The CellProfiler pipeline analysis of cell migration.

We demonstrate herein a refined method to evaluate the migration capacity of monolayer cells using the CellProfiler pipeline. We used MDA-MB-231 cells, a triple-negative breast cancer cell line, as a model to perform the wound healing assay and proceeded with the pipeline analysis. In order to see a contrast in our analysis of cell migration, we treated the cells with 10 µM kartogenin for 48 h and compared the result to the control cells treated with 0.

RUNX1 as a Novel Molecular Target for Breast Cancer.

RUNX1 has long known for its role in hematopoiesis until recently it is implicated in human breast cancer pathogenesis. This has drawn attention in research as elevated expression of RUNX1 has been observed in invasive breast cancer, and mutations of the RUNX1 gene and its binding partner CBFβ have been identified in luminal breast cancer patients, many of which have attributed to the development and progression of the disease. Increasing number of evidence also shows the involvement of RUNX1 in breast cancer migration and invasion that may lead to breast cancer metastasis.

A role for CBFβ in maintaining the metastatic phenotype of breast cancer cells.

Epithelial to mesenchymal transition (EMT) is a dynamic process that drives cancer cell plasticity and is thought to play a major role in metastasis. Here we show, using MDA-MB-231 cells as a model, that the plasticity of at least some metastatic breast cancer cells is dependent on the transcriptional co-regulator CBFβ. We demonstrate that CBFβ is essential to maintain the mesenchymal phenotype of triple-negative breast cancer cells and that CBFβ-depleted cells undergo a mesenchymal to epithelial transition (MET) and re-organise into acini-like structures, reminiscent of those formed by epithelial breast cells.