Anticancer Activities of DNA-Alkylating Pyrrole-Imidazole Polyamide Analogs Targeting RUNX Transcription Factors against p53-Mutated Pancreatic Cancer PANC-1 Cells

The runt-related transcription factor (RUNX) family is known to play important roles in the progression of Cancer. Conjugate 1, which covalently binds to the RUNX-binding sequences, was reported to inhibit the binding of RUNX proteins to their target sites and suppress Cancer growth. Here, we evaluated the Anticancer effects of 1 and its analogs 2-4 against p53-mutated PANC-1 pancreatic Cancer cells. We found that they possessed different DNA-alkylating properties in vitro. And conjugates 1-3 were shown to have Anticancer effects by inducing Apoptosis in PANC-1 cells. Furthermore, conjugates 2 and 3 suppressed Cancer growth in PANC-1 xenograft mice, with activity equivalent to a 50-fold dose of gemcitabine. Especially, 3 showed the highest alkylation efficiency, specificity, and better Anticancer effects against pancreatic Cancer than 1 in vivo without significant body weight loss. Our results revealed the potential of our compounds as new candidates for Cancer therapy.