A potent small-chemical MBD2 inhibitor, KCC-07, induces selective cytotoxicity in hepatocellular and prostate cancer cells.

BACKGROUND

Methyl-CpG-binding domain protein 2 (MBD2) is a key epigenetic regulator implicated in tumorigenesis by repressing tumor suppressor genes by recognizing DNA methylation marks and recruiting specific histone-modifying enzymes and chromatin remodeling complexes. Although KCC-07 has been identified as a potent selective MBD2 inhibitor, its cytotoxic effects on various cancer cells remain largely unexplored. In the current study, we have examined the anti-proliferative and cytotoxic activities of KCC-07 on breast cancer (MCF-7), prostate cancer (PC-3), hepatocellular carcinoma (Huh-7), and osteosarcoma (U2-OS) cell lines, along with human skin fibroblasts (HFF-1) as a non-malignant control.

METHODS AND

RESULTS

Treatment of these cells with KCC-07 induced dose- and time-dependent cytotoxicity, notably reducing viability in Huh-7 and PC-3 cells. Flow cytometry analyses revealed that KCC-07 primarily triggered necrosis in Huh-7 and apoptosis in PC-3 cells. Furthermore, KCC-07 substantially downregulated MBD2-associated oncogenic targets such as WNT1, CCND1, and ERK1/2 in Huh-7 and PC-3 cells without altering MBD2 transcription.

CONCLUSION

These findings suggest that KCC-07 elicited a considerable cytotoxicity on cancer cells, likely modulating the expression of MBD2-related genes, highlighting its potential as a candidate for cancer therapy.