Planta Med 2016; 82 - PB3
DOI: 10.1055/s-0036-1578651

Tumor/Patient Specific Action Of Various Natural Products On Cancer Stem Cells And Bulk Tumor Cells

P Balachandran 1, 2, J Zhang 1, 2, A Rimando 4, PP Claudio 1, 2, DS Pasco 1, 2, 3
  • 1National Center for Natural Products Research
  • 2Research Institute of Pharmaceutical Sciences
  • 3Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677, USA
  • 4Natural Products Utilization Research Unit, ARS, U.S. Department of Agriculture, University, Mississippi 38677, USA

Genetic and epigenetic events that contribute to the transformation of normal cells into cancerous cells, result in the abnormal functioning of many signalling pathways that control cell metabolism, proliferation, mobilization, differentiation and death. This realization has led to the search for agents that target these pathways. We have collected a battery of 13 inducible luciferase reporter gene vectors, where expression is driven by enhancer elements that bind to specific transcription factors. Several thousand crude plant extracts and pure compounds were run through this screen using HeLa cells. Several compounds viz., pterostilbene, parthenolide, apigenin and the paw extract, rich in acetogenins, exhibited diverse activity profiles using this battery and were subsequently tested in the ChemoID assay [1], against patient-derived bulk tumor cells and cancer stem-like cells. These cells were isolated from patients bearing non-small cell lung cancer, triple negative breast cancer or temodar-resistant glioblastoma multiforme. The natural products tested demonstrated either patient or tumor-type specificities for bulk vs. tumor stem-like cells in vitro. Paw extract and parthenolide showed either additive or more than additive cytotoxicity in combination with many chemotherapeutic agents. Pterostilbene reduced the effectiveness of some chemotherapeutic agents. This represents an approach that could afford us an important and unique niche in the precision medicine initiative – identifying patient/tumor-specific natural product-chemotherapeutic combinations that are effective against both bulk tumor cells and tumor stem-like cells.

Reference: [1] Mathis SE., et al. (2014) PLoS ONE 9(8): e105710. doi:10.1371/journal.pone.0105710.

This work was supported in part by a contract from the University of Mississippi Medical Center Cancer Institute and the USDA Agricultural Research Service Specific Cooperative Agreement No. 58 – 6408 – 2-0009.