Abstract 1586: Toxicity screening, apoptosis hallmark events and nitro reduction of novel quinolinium salts (BQS) on lymphoma cells

The main purpose of this research was to evaluate the effects of two novel benzazolo[3,2-a]quinolinium salts (ABQ-48 and NBQ48) on lymphoma cells (TOLEDO). The cationic nature of these BQS can facilitate its interaction with cell organelles such as mitochondria and DNA. To determine its potential cytotoxic effects the compounds were screened through the NCI 60 cell line protocol which determines the cell viability inhibitory activity in various cancer histological types. The IC50 dose for these compounds was determined and used to assess their apoptosis induction capacity evaluating apoptosis hallmark events such as DNA Fragmentation, Caspase 3&7 activators and mitochondrial membrane permeabilization. Additionally cell reduction potential of the compounds was measured. Results from the NCI 60 cell line protocol demonstrated the toxicity of BQS in multiple cancer types including breast and colon cancer cells. Preliminary results indicated mitochondrial membrane permeabilization on cells treated with NBQ48 (51.3%) and ABQ48 (57.67%) comparable to the positive controls camptothecin (51.6%) and valinomycin (55.3%). Treated cells also presented DNA fragmentation with NBQ48 and ABQ48 (28%) comparable to the positive control 37%. Preliminary data for caspases 3&7 activation strongly suggest an intrinsic apoptosis pathway. Analysis of the reduction of nitro substituted compound NBQ 48 to the amino substituted ABQ 48 on treated cells was determined by measuring an increment on fluorescence emission, characteristic of an amino specie. In conclusion, the study provides evidence of the induction of key apoptotic events as part of the mechanism of action of these novel BQS. Citation Format: Karoline Rios-Rodriguez, Jessica Soto, Christian Velez, Osvaldo Cox, Juan P. Rivera, Beatriz Zayas. Toxicity screening, apoptosis hallmark events and nitro reduction of novel quinolinium salts (BQS) on lymphoma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1586. doi:10.1158/1538-7445.AM2014-1586