Constituents of Brazilian red propolis and their preferential cytotoxic activity against human pancreatic PANC-1 cancer cell line in nutrient-deprived condition

Abstract

Human pancreatic cancer cells such as PANC-1 are known to exhibit marked tolerance to nutrition starvation that enables them to survive for prolonged period of time even under extremely nutrient-deprived conditions. Thus, elimination of this tolerance to nutrition starvation is regarded as a novel approach in anticancer drug development. In this study, the MeOH soluble extract of Brazilian red propolis was found to kill 100% PANC-1 cells preferentially in the nutrient-deprived condition at the concentration of 10 μg/mL. Further phytochemical investigation led to the isolation of 43 compounds including three new compounds, (6a S,11a S)-6a-ethoxymedicarpan ( 1), 2-(2′,4′-dihydroxyphenyl)-3-methyl-6-methoxybenzofuran ( 2), and 2,6-dihydroxy-2-[(4-hydroxyphenyl)methyl]-3-benzofuranone ( 3). Among them, (6a R,11a R)-3,8-dihydroxy-9-methoxypterocarpan ( 21, DMPC) displayed the most potent 100% preferential cytotoxicity (PC 100) at the concentration of 12.5 μM. Further study on the mode of cell death induced by DMPC against PANC-1 cells indicated that killing process was not accompanied by DNA fragmentation, rather through a nonapoptotic pathway accompanied by necrotic-type morphological changes.