The vitality of tumor cells and the ROS emission after treatment with benzimidazole substitutes and somatostatin analogs

Abstract

Background: A synthesized 1,3-disubstituted-2,3-dihydro-2-iminobenzimidazole M1 has been chosen because of its most pronounced antiproliferative effect (preliminary studies) to human colorectal cancer cell line HT-29,  breast cancer cells MDA-MB-231 and not toxic to normal Lep 3,  determined using the in vitro proliferative MTS-test. It is believed that this   suppressive activity is due to its antioxidant capacity. Other two new linear somatostatin analogs which contain hydrophobic amino-acids 3c (D-Phe-c(Cys-Phe-D-Trp-Lys-Tle-Cys)-Thr-NH₂) and 3L (Pro-Phe-Val-Tyr-Leu-Ile-D-Trp-Lys-Tle-Thr-NH₂) were tested for their toxicity to the same cells and all experiment substances were tested to activated macrophages. Methods: the ROS-scavenging ability was examined (by HORAC and ORAC) using the same cells and the obtained results confirmed a considerable suppressive capacity of the compounds. Results: The last two compounds exerted the most pronounced inhibition of the tumor cell vitality (up to 77%) at higher concentrations and were not toxic to normal Lep-3 cells.

After similar incubations with the substances activated human peritoneal macrophages displayed also emission of ROS determined by chemiluminiscence (CL). Compound M1 showed pronounced activity against activated peritoneal macrophages (PMA) mainly in the 100000x dilution in comparison to the HORAC and ORAC; 3L is most effective  only in the 100x concentration. Conclusion: All tested compounds showed different suppressive activity depending on the cell line and on the substances amount applied using HORAC / ORAC and CL.