Induction of cancer cell-specific cell death by novel cyclic naphthalene diimide derivatives

Abstract

Recently, it became clear that guanine-rich DNA sequences could form characteristic four-stranded structure (G4). As G4 is frequently found in chromosomal telomere regions and in the promotor region of cancer-related genes, G4 is expected to be a target for developing new anticancer drugs. In this study, we compared cytotoxic effect of cyclic naphthalenediimide derivative (cNDI) that specifically bind to G4, with a widely-used anticancer drug cisplatin (CDDP).

Human oral cancer cell line SAS and the human normal oral keratinocyte cells (HOK) were treated with either cNDI or CDDP and cell viability was assessed by WST-8 assay. Both cNDI and CDDP dose-dependently decreased cell viability of the cells. The ED₅₀ values of cNDI on SAS and HOK were 0.05 and 1.09 microM, respectively, while those of CDDP on the cells were 2.08 and 5.39 microM. Both cNDI and CDDP induced apoptosis that was assessed by AnnexinV-staining and cleavage of PARP and procaspase-3 assessed in Western blotting. Expression level of c-Myc and TERT mRNA was decreased in SAS cells treated by cNDI, but not by CDDP.

The results suggested that cNDI induced apoptosis with high specificity to cancer cells compared to CDDP. Thus, cNDI is considered to be promising as new anticancer agents with improved cancer specificity and low adverse effect.