Abstract 2144: Anti-tumor activity of polyphenols from seaweeds: First-hand evidence on the efficacy, molecular targets and mode of action for multifarious extractions from five different brown-algae against pancreatic cancer.
Authors: Aravindan Sheeja , Delma Caroline R. , Thirugnanasambandan Somasundaram S. , Natarajan Mohan , Herman Terence S. , Aravindan Natarajan 
Published: August 2014

Abstract
Pancreatic cancer remains the fourth leading cause of cancer death with an unacceptable survival that has remained relatively unchanged over the past 25 years. The presence of occult or clinical metastases at the time of diagnosis together with the lack of effective chemotherapies pose a dire need for designing new and targeted therapeutic deliverables that favors the clinical outcome. Herein, we investigated the anti-tumorigenic potential of polyphenols from five different brown-algae in human pancreatic cancer cells (MiaPaCa-2, Panc-1, BXPC-3 and Panc-3.27). Total anti-oxidant capacity (TAC) analysis on stepwise polyphenol separations with increasing polarity (Hexane-DCM-EA-methanol) identified high levels of TAC in DCM and EA extractions across all seaweeds assessed. All DCM and EA separated polyphenols induced a dose-dependent inhibition of cell proliferation. Further, these polyphenols profoundly inhibited cell viability (assessed by trypan blue exclusion) and enhanced DNA damage (determined by acridine orange/Ethidium bromide staining and DNA fragmentation) in all the cell lines investigated. More importantly, luciferase reporter assay revealed a significant inhibition of NFκB transactivation in cells treated with polyphenols. Interestingly, QPCR analysis identified a differential yet definite regulation of pro-tumorigenic EGFR, VEGFA, AKT, hTERT, kRas, Bcl2, FGFa and PDGFa transcription in cells treated with DCM and EA polyphenols. Immunoblotting validates the inhibitory potential of seaweed polyphenols in EGFR phosphorylation, kRas and Stat3. Together, these data suggest that intermediate polarity based fractions of seaweed polyphenols may significantly potentiate tumor cell killing and may serve as potential drug deliverable for pancreatic cancer cure. To that end, these data strongly imply that at least in pancreatic cancer cells, these fractions may target more than one signaling cascade. Further the data clearly identifies three fractions that are relatively more potent than other fractions and may serve as the “deliverable” in this setting. More Studies dissecting out the active constituents in potent fractions, mechanisms of action and synergism, if any, are warranted and are currently in the process.
Citation Format: Sheeja Aravindan, Caroline R. Delma, Somasundaram S. Thirugnanasambandan, Mohan Natarajan, Terence S. Herman, Natarajan Aravindan. Anti-tumor activity of polyphenols from seaweeds: First-hand evidence on the efficacy, molecular targets and mode of action for multifarious extractions from five different brown-algae against pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2144. doi:10.1158/1538-7445.AM2013-2144