Bioactive phlorotannin as autophagy modulator in cervical cancer cells and advanced glycation end products inhibitor in glucotoxic C. elegans

Abstract

Brown algae produce varieties of potent metabolites in order to adapt to extreme environment. Among these metabolites, polyphenols comprised of phlorotannins serve as powerful multifaceted bioactive with vast pharmacological potentials against non-communicable diseases like cancer and diabetes. In this study, a new phlorotannin was extracted from Padina tetrastromatica and characterized by Fourier Transform-Infrared, Nuclear Magnetic Resonance & Electronspray Ionization-Mass Spectroscopy. The phlorotannin exhibited potent DPPH and nitric oxide radical-scavenging activity in in-vitro, which were better than the standard antioxidants and other phlorotannins, previously reported. Further, the novel phlorotannin explicitly inhibited advanced glycation end-products formation in both in-vitro and in-vivo studies using hyperglycaemic C. elegans as an animal model and confirmed by live-cell fluorescence imaging. In addition, a significant modulation in expression of stress-responsive genes daf-2 and daf-16 were observed in phlorotannin treated hyperglycemic C. elegans. Moreover, the cytotoxic potential of phlorotannin (2,4,6-trioxa-1,3,5(1,3) tribenzenacyclohexaphane-15,35,55-triol) was explored for the first time in human cervical cancer cells (HeLa) and interesting observation was made that the cancer cell death was induced by activation of autophagy and pro-apoptotic protein markers i.e., LC3I/II, p21 and p53 that were confirmed by western-blot technique. Therefore, phlorotannin can be postulated as a potential bioactive for oxidative stress-mediated diseases, including diabetes and cancer.