The search for novel treatment agents for pancreatic cancer : tales from the land and sea

![CDATA[Background: Pancreatic cancer (PC) is a disastrous disease with a dismal survival rate of only 5%. The current standard of care for PC patients consists of surgery and/or treatment with gemcitabine, a natural product‐derived chemotherapeutic which has been shown to have a modest effect for some patients, however it is not a long‐term curative treatment and results in many unwanted side effects. Natural therapies have the advantage of being relatively inexpensive to manufacture and are usually very tolerable and effective. Therefore, there is a strong need for novel, naturally occurring therapeutic options for PC. Aim: To determine if crude extracts and/or purified compounds from various Australian and South East Asian flora and fauna (Vietnamese medicinal plants, Blueberry ash, bitter melon, Eucalyptus and marine invertebrates) exert anti‐cancer activity in vitro, with an emphasis on pancreatic cancer. Methods: Pancreatic cancer cell lines (BxPC3, MiaPaCa2 and CFPAC‐1) and normal human pancreatic epithelial cells (HPDE) were treated with varying doses of crude extracts and purified compounds over a range of treatment times. Cell viability was assessed using CCK8 and MTT viability assays to determine the extent of anti‐cancer activity due to growth inhibition and/or apoptosis. Results: Significant growth inhibition of pancreatic cancer cells was observed with the purified compound pristimerin (from 2 Vietnamese medicinal plants), which displayed an IC50 of <2.7 uM in pancreatic cancer cell lines compared to 4.9 uM in normal HPDE cells. Crude extracts also showed significant selective efficacy at concentrations below 100 μg/mL; such as blueberry ash extract with IC50 values of 38.53 ug/mL and 57.34 ug/mL in BxPC3 pancreatic cancer cells and HPDE cells respectively; saponin enriched bitter melon extract IC50 values were 11.02 μg/mL and 54.60 μg/mL for MiaPaCa2 and HPDE cells, respectively; while specific Eucalypt crude extracts showed very low IC50 values (7‐11 μg/mL in MiaPaCa2 cells). Further, 2 semi‐purified compounds from a marine invertebrate had IC50 values <12.5 μg/mL for MiaPaCa‐2 cells and >25 μg/mL for HPDE cells. Conclusions: Purified compounds and crude extracts from plants and marine invertebrates show significant selective pancreatic cancer growth inhibition in vitro at concentrations with minimal effect on normal pancreatic cells, therefore showing promise as novel anti‐pancreatic cancer therapies.]]