Pancreatic cancer is one of the deadliest forms of cancer, resulting in 44,330 deaths a year in the United States alone. It is exceptionally aggressive with a five-year survival rate of 8.5%. Three main factors contribute to low pancreatic cancer survival rates: the location of the pancreas makes surgical treatment difficult; cancer cells show resistance to conventional chemotherapies; and lack of early detection complicates treatment further. Therapies currently in place barely extend life expectancy by a year, and while these numbers are improving, more effective treatments are still necessary to improve outcomes.<br/>Researchers discovered the natural product angelmarin from the root of the medicinal plant <i>Angelica pubescens. </i>Angelmarin demonstrated 100% preferential cytotoxicity against pancreatic cancer cells under nutrient-deprived conditions. Because pancreatic cancer cells grow under these conditions naturally, this discovery was promising. Based on the core structure of angelmarin, our research group designed and synthesized several structural analogs of the natural product resulting in our current lead compound, DCM-MJ-I-21. Our studies showed that DCM-MJ-I-21 is highly selective and potent, killing 100% of PANC-1 cells under nutrient-deprived conditions at approximately 12.5 uM. In this study, further investigations into the pancreatic anticancer activity of our lead compound were conducted. Specifically, comparative studies between our lead compound and a commercially available, specific autophagy inhibitor against PANC-1 cells under nutrient-deprived and nutrient-rich conditions will be presented.

Investigations into pancreatic anticancer activity of DCM-MJ-I-21 isoprenylated coumarin

2019 Spring National Meeting

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