Pancreatic cancer is primarily found in the pancreatic duct, and the histological subtype that is most commonly associated with this cancer is adenocarcinoma, which has a notoriously poor prognosis. According to medical research, pancreatic cancer has a propensity to metastasize in the lymph nodes and liver that are situated near the pancreas, and this tends to happen at an early stage of life.
The progression and metastasis of cancer are ultimately due to the circumvention of targeted therapies caused by molecular crosstalk between cell signaling pathways. Thus, the requirement arises to devise more powerful treatment procedures, which incorporate the discovery of new anti-tumor components from natural sources, with minimum side effects. In recent years, Fucoidan, a marine-derived product with low toxicity, has garnered the attention of global researchers who aim to develop more potent anticancer agents.
Pancreatic cancer (PC) is known to have a poor prognosis, possibly because of its resistance to apoptosis and its tendency for early systemic dissemination. More than 50% of PCs have p53 mutations, and NFκB is constitutively activated in treatment-resistant residual disease. These mutations and activations avoid cell death and metastasis.
Hence, I would like to share the study, “Fucoidan from marine brown algae attenuates pancreatic cancer progression by regulating p53 – NFκB crosstalk” by Caroline R. et al.
The above-mentioned study has demonstrated the anti-PC potential of a fucoidan extract from a marine brown alga, Turbinaria conoides (J. Agardh) Kützing (Sargassum family). The primary focus of our study was to carefully characterize the active fraction of fucoidan extract, in order to identify its superior anti-PC effects and shed light on the underlying mechanisms. The potential of five fucoidan fractions, which were isolated by ion exchange chromatography, was tested in genetically diverse human PC cell lines. All fractions exerted significant dose-dependent and time-dependent control of cell survival. Fucoidan-induced apoptosis activated caspases-3, -8, and -9, and cleaved poly ADP-ribose polymerase (PARP). Pathway-specific transcriptional analysis revealed fucoidan inhibition of 57 and 38 nuclear factor-κB (NFκB) pathway molecules in MiaPaCa-2 and Panc-1 cells, respectively. (See Figure. 1)
In addition to its other benefits, fucoidan F5 was found to have the ability to inhibit both constitutive and tumor necrosis factor-α (TNFα)-mediated NFκB DNA-binding activity in PC cells. Upregulation of cytoplasmic IκB levels and a significant decrease in NFκB-dependent luciferase activity further demonstrate the inhibitory capacity of seaweed fucoidan on NFκB. Moreover, administering fucoidan caused an increase in cellular p53 in PC cells and reversed the decrease in p53 caused by NFκB expression. This result suggests that fucoidan regulates PC progression and that fucoidan may target p53-NFκB crosstalk to determine the apoptosis of her PC cells. The study demonstrated how a fucoidan fraction chosen from the marine brown alga Turbinaria conoides possesses anti-PC potential. Their results revealed that fucoidan negatively regulates NFκB signaling and induces apoptosis in PC cell lines by activating p53.
To conclude, the study reveals that fucoidan obtained from Turbinaria conoides could be a promising therapeutic agent that can inhibit the proliferation of PC cells and trigger apoptosis by activating the caspase-dependent intrinsic and extrinsic pathways. Furthermore, NFκB signaling is negatively regulated by fucoidan via inhibition of both constitutive and TNF-α-mediated NFκB activation. Fucoidan also increases the expression of the tumor suppressor p53 and induces apoptosis in PC cells in an NFκB inhibition-dependent manner. By considering all the findings, it is evident that fucoidan has the potential to act as an anti-PC agent.
Source: Phytochemistry Volume 167, November 2019, 112078