Pancreatic cancer is one of the deadliest cancers, with a 5-year survival rate of 9% and a median survival time of only 10 to 12 months. Contributors to its lethality include late diagnosis due to lack of early detection methods and a nutrient-deprived tumor microenvironment that supports aggressive tumor growth. These severely limit therapy options available to patients at the time of diagnosis, making the development of a novel, effective treatment against pancreatic cancer a priority in the field of cancer research. Our lab has synthesized isoprenylated coumarin derivatives based on the coumarin scaffold from the natural product angelmarin that exhibit preferential cytotoxic activity in nutrient-deprived conditions against the pancreatic cancer cell line PANC-1. Research into the mechanism of action of our compounds determined that they work as autophagy inhibitors, as autophagy promotes tumorigenesis in pancreatic cancer cells. Autophagy has also been shown to promote tumorigenesis in lung, colon, breast, prostate, and ovarian cancers. This research investigates the activity of our isoprenylated compounds on non-pancreatic cancer cell lines for cytotoxic activity and confirms the results using molecular biology techniques to look at cell signaling pathways related to autophagy inhibition.

Investigating the activity and mechanism of natural product derivatives against multiple cancer types

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ACS Spring 2023

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