Pancreatic cancer (PC) 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 PC 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 and sustained (time-independent) inhibition of cell proliferation and viability. Further, these polyphenols profoundly enhanced DNA damage (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 transcription in cells treated with polyphenols. Interestingly, QPCR analysis identified a differential yet definite regulation of pro-tumorigenic EGFR, VEGFA, AKT, hTERT, kRas, Bcl2, FGFα and PDGFα transcription in cells treated with DCM and EA polyphenols. Immunoblotting validates the inhibitory potential of seaweed polyphenols in EGFR phosphorylation, kRas, AurKβ 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 PC cure. More Studies dissecting out the active constituents in potent fractions, mechanisms of action and synergism, if any, are warranted and are currently in process.

Alzheimer's disease (AD) is one of the most common chronic neurodegenerative diseases and is associated with two types of pathological hallmarks in the brain. These biomarkers are extracellular plaque deposits mainly composed by amyloid-beta (Aβ) peptides and intracellular neurofibrillary tangles (NFT) formed by tau hyperphosphorylation [1]. Aβ peptides are deposited through enzymatic cleavage of amyloid precursor protein (APP) by β and γ-secretase enzymes [2]. In 2017, the Alzheimer's Association surveyed the AD population worldwide and found 48 million people with early symptoms of the disease. The prevalence of the disease is expected to double by 2050. The most common symptoms are short-term memory loss, difficulty in finding words, trouble with visual-spatial understanding, reasoning, judgment and insight.Reactive oxygen species (ROS) are the major key molecules in neurodegenerative diseases. Hydrogen peroxide (H 2 O 2 ) exposure in cultured neuronal cells would cause an imbalance of ROS production and scavenging activities. This process could be widely used to study this oxidative stress inducer in cell line models [3]. H 2 O 2induced oxidative stress can cause hyperphosphorylation in tau protein and induce formation of toxic neurofibrillary tangles in the brain cells [4]. In addition, all-trans-retinoic acid (RA) induction would enhance the neuronal morphological differentiation of SH-SY5Y cells and augment Alzheimer's disease markers such as tau and GSK3-β expression [5]. Hence, H 2 O 2 -induced pathogenicity and RA differentiation in SH-SY5Y cells could serve as a suitable model system for studying neuronal cell degeneration. Epalrestat (EPS) is a brain penetrant aldose reductase inhibitor, an approved drug currently used for the treatment of diabetic neuropathy. At near-plasma concentration, EPS induces glutathione biosynthesis, which in turn reduces oxidative stress in the neuronal cells. In this study, we found that EPS reduces neurodegeneration by inhibiting reactive oxygen species (ROS)-induced oxidative injury, mitochondrial membrane damage, apoptosis and tauopathy. EPS treatment up to 50 μM did not show any toxic effect on SH-SY5Y cell line (neuroblastoma cells). However, we observed toxic effect at a concentration of 100 μM and above. At 50 μM concentration, EPS showed better antioxidant activity against H 2 O 2 (100 μM)-induced cytotoxicity, ROS formation and mitochondrial membrane damage in retinoic acid-differentiated SH-SY5Y cell line. Furthermore, our study revealed that 50 μM of EPS concentration reduced the glycogen synthase kinase-3 β (GSK3-β) expression and total tau protein level in H 2 O 2 (100 μM)-treated cells. Findings from this study confirms the therapeutic efficacy of EPS on regulating Alzheimer's disease (AD) by regulating GSK3β and total tau proteins phosphorylation, which helped to restore the cellular viability. This process could also reduce toxic fibrillary tangle formation and disease progression of AD. Therefore, it is our view that an optimal concentration of EPS therapy...

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In our previous work, we assessed the ameliorative effect of crude extract from Padina boergesenii. In this report, we have extended these study by fractionating the methanol extract with methanol:ethylacetate (1:3,v/v) (MME-F) and assessed the cytotoxic effect of MME-F fraction in human renal carcinoma cell lines (A498 and ACHN). The fraction had time-and dose-dependent inhibition of cancer cell proliferation, migration with deceleration of cancer growth at EC -22.73 μg in A498 and 26.43 μg in ACHN cells. Cells treated at EC value 25 μg displayed twofold greater ability to induce early and late stage of apoptosis. The cells treated with polyphenolic fraction (MME-F) induced cell cycle arrest at G2/M phase. HPLC/DAD chromatographic procedures quantified polyphenols from active fraction (MME-F). These data revealed the functional activity of polyphenols from brown alga, P. boergesenii as a potent inhibitor of cancer proliferation with induction of apoptosis, it suggest their applicability in preventing cancer metastasis.