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Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
Network-Based Analysis of Nutraceuticals in Human Hepatocellular Carcinomas Reveals Mechanisms of Chemopreventive
M Michailidou1, I N Melas2, D E Messinis3
1GP Livanos and M Simou Laboratories, 1st Department of Critical Care Medicine & Pulmonary Services, Evangelismos Hospital, Medical School, University of Athens Athens, Greece.
Abstract:
Chronic inflammation is associated with the development of human hepatocellular carcinoma (HCC), an essentially incurable cancer. Anti-inflammatory nutraceuticals have emerged as promising candidates against HCC, yet the mechanisms through which they influence the cell signaling machinery to impose phenotypic changes remain unresolved. Herein we implemented a systems biology approach in HCC cells, based on the integration of cytokine release and phospoproteomic data from high-throughput xMAP Luminex assays to elucidate the action mode of prominent nutraceuticals in terms of topology alterations of HCC-specific signaling networks. An optimization algorithm based on SigNetTrainer, an Integer Linear Programming formulation, was applied to construct networks linking signal transduction to cytokine secretion by combining prior knowledge of protein connectivity with proteomic data. Our analysis identified the most probable target phosphoproteins of interrogated compounds and predicted translational control as a new mechanism underlying their anticytokine action. Induced alterations corroborated with inhibition of HCC-driven angiogenesis and metastasis.
Insights
This study reveals how anti-inflammatory nutraceuticals combat hepatocellular carcinoma (HCC) by altering cell signaling networks. The findings uncover a new mechanism of translational control impacting HCC progression.
Area of Science:
- Oncology
- Systems Biology
- Pharmacology
Background:
- Chronic inflammation is a key driver of hepatocellular carcinoma (HCC), a challenging human cancer.
- The precise molecular mechanisms by which anti-inflammatory nutraceuticals exert anti-HCC effects are not fully understood.
- Investigating these mechanisms is crucial for developing novel therapeutic strategies against HCC.
Purpose of the Study:
- To elucidate the action mode of prominent nutraceuticals in hepatocellular carcinoma (HCC) cells.
- To identify alterations in HCC-specific signaling networks induced by nutraceuticals.
- To uncover novel mechanisms of nutraceuticals' anti-cancer effects.
Main Methods:
- A systems biology approach integrating cytokine release and phosphoproteomic data.
- High-throughput xMAP Luminex assays for data acquisition.
- SigNetTrainer, an Integer Linear Programming formulation, for network construction and analysis.
Main Results:
- Identified key phosphoprotein targets of the studied nutraceuticals.
- Predicted translational control as a novel mechanism for nutraceuticals' anti-cytokine action.
- Demonstrated that induced network alterations inhibit HCC-driven angiogenesis and metastasis.
Conclusions:
- Nutraceuticals modulate HCC cell signaling networks through mechanisms including translational control.
- This research provides a deeper understanding of nutraceuticals' therapeutic potential against HCC.
- The findings support the development of nutraceutical-based interventions for HCC treatment and prevention.
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