Antiproliferative effects of benzimidazole derivatives on 2D and 3D cell cultures

Uvod: Karcinom dojke predstavlja vodeći uzrok smrtnosti od raka kod žena diljem svijeta. Kontinuirano se provode istraživanja na novim modelima, poput 3D staničnih sustava, sa svrhom razvijanja učinkovitijih antitumorskih lijekova. Neki od njih su i benzimidazoli, čija je jezgra dio mnogih terapeutskih agensa, a mehanizam djelovanja usmjeren je izravno na tumorske stanice, pa pogoduju daljnjim istraživanjima kao potencijalni citostatici. Ciljevi: Ispitati razlikuje li se antiproliferativni potencijal derivata benzimidazola na staničnim linijama karcinoma dojke u 2D i 3D staničnoj kulturi. Odrediti promjene u staničnom ciklusu. Materijali i metode: Inhibitorni učinak derivata benzimidazola na rast MDA-MB-231 i MCF-7 tumorskih stanica dojke određen je MTT testom u 2D i 3D kulturi. Promjene u staničnom ciklusu ispitivanih staničnih linija praćene su protočnim citometrom. Rezultati: Uočene su razlike između antiproliferativnog učinka derivata benzimidazola na stanice koje rastu u 2D kulturi u odnosu na 3D kulturu. Najbolju inhibiciju na rast stanica ostvario je derivat MB-129 na obje stanične linije pri koncentraciji 1x10-4 M. Zabilježene su promjene u udjelu stanica u pojedinim fazama staničnog ciklusa; na MCF-7 stanicama derivat MB-123 je uzrokovao njihovo nakupljanje u G1-fazi, a na staničnu liniju MDA-MB-231 najznačajnije je djelovao spoj MB-129 koji dovodi do povećanja broja stanica u S fazi. Zaključak: Derivati benzimidazola pokazuju antiproliferativne učinke na rast stanica karcinoma dojke, ovisno o primijenjenoj koncentraciji i uvjetima kulture. Statistički najznačajniji učinak je imao derivat MB-129. Izloženost tumorskih stanica ispitivanim derivatima je dovela do promjena u staničnom ciklusu.Introduction: Breast cancer is the leading cause of cancer death in women all around the world. The research on new models, such as 3D cell systems, is ongoing, with the aim of developing effective anticancer drugs. One of them is benzimidazole, the core of which is a part of many therapeutic agents, and the mechanism of action directly focuses on tumor cells, thus favoring further research as potential cytostatic. Objectives: To investigate whether the antiproliferative potential of benzimidazole derivatives on the breast cancer cell lines differs in 2D and 3D cell cultures. To determine changes in the cell cycle. Materials and methods: The inhibitory effect of benzimidazole derivatives on MDA-MB-231 and MCF-7 tumor cell growth rates was determined by MTT test in 2D and 3D cultures. Changes in the cell cycle of the examined cell lines were monitored by flow cytometry. Results: Differences between the antiproliferative effects of benzimidazole derivatives on the cell growth in 2D culture compared to 3D culture were observed. The best growth inhibition of the cell growth resulted in the MB-129 derivative on both cell lines at 1x10-4 M concentration. Cell-specific changes in individual phases of the cell cycle were recorded; on MCF-7 cells, the MB-123 derivative caused their accumulation in the G1-phase, and the MDA-MB-231 cell line was the most important compound MB-129 leading to accumulation of cells in the S-phase of the cycle. Conclusion: Benzimidazole derivatives exhibit antiproliferative effects on the breast cancer cell growth, depending on the concentration applied and culturing conditions. MB-129 derivative had statistically most significant effect. Exposure of the cells to the investigated derivatives has led to changes in the cell cycle