1. Academic Validation
  2. Pterostilbene, An Active Constituent of Blueberries, Suppresses Proliferation Potential of Human Cholangiocarcinoma via Enhancing the Autophagic Flux

Pterostilbene, An Active Constituent of Blueberries, Suppresses Proliferation Potential of Human Cholangiocarcinoma via Enhancing the Autophagic Flux

  • Front Pharmacol. 2019 Oct 22;10:1238. doi: 10.3389/fphar.2019.01238.
Dong Wang 1 2 Haoran Guo 2 3 Huahong Yang 4 Dongyin Wang 1 Pujun Gao 1 Wei Wei 2 3
Affiliations

Affiliations

  • 1 Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, China.
  • 2 Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, China.
  • 3 Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, China.
  • 4 Department of Respiration, The First Hospital of Jilin University, Jilin University, Changchun, China.
Abstract

Background: Human cholangiocarcinoma (CCA) is a highly lethal Cancer that occurs in the biliary tract. It is characterized by early invasion, poor outcomes, and resistance to current chemotherapies. To date, an effective therapeutic strategy for this devastating and deadly disease is lacking. Pterostilbene, a natural compound found in the extracts of many Plants including blueberries, kino tree, or dragon blood tree, has several health benefits. However, its effects on CCA have not been clarified. Here, we investigated the potential application of pterostilbene for the treatment of human CCA in vitro and in vivo. Methods: The effects of pterostilbene on CCA cells were determined by assessing cell viability (CCK), cell proliferation, and colony formation. Cell cycle arrest and Apoptosis were measured by flow cytometric analysis, whereas proteins related to Autophagy were detected by immunofluorescence and immunoblotting assays. A well-established xenograft mouse model was used to evaluate the effects of pterostilbene on tumor growth in vivo. Results: Pterostilbene induced dose-dependent and time-dependent cytotoxic effects, inhibited proliferation and colony formation, and caused S phase cell cycle arrest in CCA cells. Instead of triggering apoptotic cell death in these cells, pterostilbene was found to exert potent autophagy-inducing effects, and this correlated with p62 downregulation, elevated expression of endogenous Beclin-1, ATG5, and LC3-II, and increases in LC3 puncta. Pretreating Cancer cells with the Autophagy Inhibitor 3-MA suppressed the induction of Autophagy and antitumor activity caused by pterostilbene. Finally, we confirmed that pterostilbene inhibited tumor growth in a CCA xenograft mouse model with minimal general toxicity. Conclusion: Taken together, our findings indicate that pterostilbene, through the induction of autophagic flux, acts as an anti-cancer agent against CCA cells.

Keywords

anti-cancer; autophagy; human cholangiocarcinoma; light chain 3; pterostilbene.

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