Seaweed polyphenols exerts autophagy dependent anti-tumor activity and promotes radio-sensitization/radio-protection in PC cells. (A) Individual gene QPCR analysis showing transcriptional modulations of ATG3, ATG5, ATG7, ATG12, LC3A, LC3B and Belcin1 in MiaPaCa-2 cells, either mock-irradiated, exposed to FIR (2Gy x 5d) or exposed to FIR and treated with 100 μg/ml of SA-EA, PT-EA, or HT-EA seaweed polyphenol fractions. Treating the radio-resistant cells with seaweed polyphenols significantly inhibited ATG3, ATG5, ATG7, ATG12, LC3A, LC3B and Belcin1 transcription in radio-resistant Panc-3.27 and MiaPaCa-2 cells. (B) Representative images of Operetta high-throughput confocal imaging showing BrdU incorporation levels in MiaPaCa-2 cells either mock irradiated, exposed to fractionated irradiation (FIR, 2Gy x 5d), exposed to seaweed polyphenols (SA-EA, PT-EA or HT-EA - 100 g/ml), exposed to each seaweed polyphenols followed by FIR or exposed to FIR followed by seaweed polyphenol treatment. Histograms obtained from Operetta integrated automated Columbus image analysis software computed BrdU incorporation for 63 different fields/well showing significant reduction in radiotherapy-induced proliferating cells with seaweed polyphenol treatment. (C) Representative images of Operetta high-throughput confocal imaging showing BrdU incorporation levels in MiaPaCa-2 and Panc-3.27 cells either mock irradiated, exposed to radiation (2Gy), LC3B silenced or LC3B silenced and exposed to IR. Histograms obtained from automated Columbus image analysis computed BrdU incorporation (for 63 different fields/well) showing significant reduction in radiotherapy-activated cell proliferation with LC3B silencing.