Salecan Suppresses Pancreatic Cancer Progression by Promoting Necroptosis via the RIPK1/MLKL Pathway

TL;DR

Salecan, a natural polysaccharide, fights pancreatic cancer by triggering cell death through the RIPK1/MLKL pathway without harming normal cells.

Contribution

Salecan induces necroptosis in pancreatic cancer cells via the RIPK1/MLKL pathway, offering a novel therapeutic strategy.

Findings

Salecan inhibits pancreatic cancer cell proliferation, migration, and invasion.

Salecan promotes necroptosis rather than apoptosis in pancreatic cancer cells.

The anti-cancer effects of Salecan are mediated through the RIPK1/MLKL signaling pathway.

Abstract

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor and leads to high human malignancy and mortality. Because PDAC is highly drug-resistant and current treatments have adverse reactions, exploring novel approaches for PDAC prevention and therapy is urgently needed. Methods: Antitumor activities of Salecan were evaluated on multiple human pancreatic adenocarcinoma cells in vitro. Cell viability, colony formation, migration and invasion, flow cytometry, caspase-3 activity, qRT-PCR and Western blotting were monitored. RNA-seq was conducted to clarify the mechanism underlying Salecan’s inhibition of pancreatic cancer cell progression. Results: Here we show that Salecan, a naturally occurring polysaccharide of β-glucan, can significantly inhibit pancreatic cancer cell proliferation and exhibit no toxicity in normal cells. We find that Salecan impedes pancreatic cancer cell migration and invasion via the epithelial-to-mesenchymal transition (EMT) pathway. Mechanistically, through RNA sequencing, we reveal that Salecan induces pancreatic cancer cell necroptosis, instead of apoptosis. Moreover, Salecan’s anti-pancreatic cancer bioactivity is attributed to its promotion of the receptor-interacting protein kinase 1 (RIPK1) and mixed lineage kinase-like (MLKL) signaling pathway. Conclusions: Salecan can inhibit pancreatic cancer cell proliferation, migration and invasion in vitro and accelerate cell death by inducing the necroptosis via the MLKL/RIPK1 pathway. These findings identify that Salecan may become a potential functional food component for preventing and treating PDAC.

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