Abstract 3220: Lichen derived polyphenols as potential anticancer drugs

Abstract

Abstract Polyphenols such as resveratrol, curcumin, (-)-epigallocatechin 3-gallate (EGCG) etc. have been shown to have anticancer properties. The anticancer activities of polyphenols include, but are not limited to, anti-oxidative effects, pro-apoptosis, DNA damage, anti-angiogenic effects, and immunostimulation. Lichens, symbiotic systems involving a fungus and an alga and/or cyanobacterium, are a rich source of polyphenols. Based on our previous research we have demonstrated that crude extracts of different lichen species affect cell proliferation, cell cycle dynamics, and cause apoptosis in Burkitt's lymphoma (Raji cells). This research examines the effects of a lichen-derived polyphenol compound, usnic acid, on human colon adenocarcinoma (HT-29) cells. We treated HT-29 cells with various concentrations (10, 30 and 50 µg/ml) of usnic acid for 24 hours. Although the viability was not affected by the treatment, there was a significant decrease in cell proliferation in dose-dependent manner. We also observed that after treatment, the morphology of treated cells was completely different from that of untreated control cells. Using transmission electron microscopy (TEM), we studied the morphological differences between control and treated HT-29 cells. The TEM micrographs clearly show that usnic acid damaged the mitochondria, reduced the amount of free ribosomes, and also distorted the shape of the nucleus. As the treatment of HT-29 with usnic acid reduced the rate of cell proliferation significantly, we investigated the effects of usnic acid on HT-29 cell cycle dynamics. Our results indicate that with the higher usnic acid concentrations (30 and 50 µg/ml) the cell cycle was stopped at the G0/G1 stage. These results further document the pattern of decreasing proliferation of HT-29 cells treated with usnic acid. With the distortion of the nucleus following exposure to usnic acid, we also investigated the effects of usnic acid on DNA the HT-29 cells. We performed a single cell gel electrophoresis (Comet Assay) to study the DNA damaging effects of various concentrations of usnic acid. Our results showed that there was a dose dependent increase in damage to the HT-29 cells' DNA resulting in 56.7% of the total DNA moving into the comet tail at 50 µg/ml concentration of usnic acid. These preliminary results suggest that lichen derived polyphenols could be a potential source of anticancer drug therapies. However, additional research is needed to further validate these findings. Citation Format: Gajendra Shrestha, Michael Xiao, Richard Robison, Larry L. St. Clair, Kim O'Neill. Lichen derived polyphenols as potential anticancer drugs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3220. doi:10.1158/1538-7445.AM2014-3220