Whole organ culture model for sodium pentaborate pentahydrate treatment of prostate cancer

Drug discovery and toxicity experiments have been performed via different cell culture models for several decades. Two dimensional (2D) cell culture model has been widely used as an in vitro technique to test drugs. However, monolayer cell culture (2D) is not suitable for metastatic colonization and evaluation of drug resistance in cancer cells in vitro. Extracellular matrix(ECM) has essential roles in angiogenesis, particularly in cancer cell invasion. Construction of in vitro cell culture models which mimic in vivo is the ideal way to solve early drug discovery issues. Acellular matrices which contain ECM components are used in 3D cell culture models in order to provide in vivo cellular phenotype and cell-matrix interactions. Energy metabolism in cancerous cell plays crucial roles in their growth, survival, proliferation, and long term maintenance. Sirtuins, known as NAD+-dependent deacetylases or ADP ribosyltransferases, regulate cell survival and change cellular energy state in cancerous cell. Protein acetylation, one of the many post-translational modification, is regulated by sirtuins in order to modulate energy-related metabolic pathways. Boron-dependent compounds have been used for the inhibition of prostate cancer proliferation in a dose-dependent manner. In addition, boric acid was also shown to interact with NAD+, which might affect NAD+/NADH ratio regulating sirtuin activity and cellular energy state. In this study, organoid cell culture model was constructed to examine the effect of sodium borate (NaB) on healthy, PNT1A, and cancer prostate cells, DU-145, and PC-3.