Evaluating Potential Novel Cancer Therapeutics Through Cell Culture-Based Assays

Cancer remains a leading cause of mortality worldwide, driven by uncontrolled cell growth and metabolic alterations that support tumor progression. Here, we report the use of cell-based assays to assess the anticancer properties of two sets of compounds of interest that target two very different biological molecules. Fatty acid synthase (FASN), an enzyme involved in fatty acid biosynthesis, is a prognostic indicator for its overexpression in various types of cancer, making it an attractive target for novel therapeutic strategies. FDA-approved drugs for various medical conditions, such as schizophrenia and hypercholesterolemia, have been computationally docked into the beta-ketoacyl reductase domain of FASN. Eight drugs were selected for further evaluation based on their observed binding energies with the FASN domain. These drugs were tested for cytotoxicity in cervical and prostate cancer cell lines and IC50 values ranging from 1.5 to 34.0 µM were observed. Additional studies are currently underway to confirm FASN inhibition as the cause of cell death. In a second project, we used similar assays to assess copper(II)-based metal complexes. Metal-based complexes, such as cisplatin, have been proven as cancer-killing drugs. Many of these complexes cause cellular damage through DNA interactions. We have developed copper-based complexes that intercalate with and cleave DNA. The complexes were evaluated for cytotoxicity in cervical and prostate cancer cell lines, many showing toxicity with IC50 values in the range of 10 to 50 µM. Further studies will focus on determining the mechanism of cell death. All of these compounds present potential therapeutic developments, aiding in the fight against cancer.