3D Screening of Lung Cancer Spheroids using Natural Products

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and is about 84% of all lung cancer cases that are diagnosed. NSCLC remains one of the leading causes of cancer-associated death, with a 5-year survival rate less of 25%. This type of cancer begins with healthy cells that change and start growing out of control forming lesions or tumors. Understanding the dynamics of how the tumor microenvironment promotes the cancer initiation and progression that will lead to the cancer metastasis is crucial to help in the process of identifying new molecular therapies. Primary cell 3D cell culture models have received renewed recognition not only due to their ability to better mimic the complexity of in vivo tumors as a potential bridge between traditional 2D culture and in vivo studies. 3D cell cultures are now cost effective and efficient and have been developed by combining the use of a cell-repellent surface and a novel angle plate adaptor technology. We also have access to one of the world’s largest repositories of Natural Products (NPs) at Scripps. NPs are typically not very well represented in the current drug discovery libraries and can provide a new insight to discover leads that could potentially emerge as novel molecular therapies. We combined these technologies for 3D cell culture primary screening in 1536 well format using ten NSCLC cells lines (5 wild type and 5 mutant) against ~1280 natural products. After further evaluation, the selected active NPs identified were prioritized to be screened against all 10 NSCLC cell lines as concentration response curves to determine the efficacy and selectivity of the compounds between wild type and mutant 3D cell models. Here, we demonstrate fully automated 3D screening using natural products that may identify NPs from microorganisms that can provide a future use toward human cancer.