Pterostilbene Inhibits the Growth of Human Esophageal Cancer Cells by Regulating Endoplasmic Reticulum Stress.

Abstract

BACKGROUND/AIMS:

Pterostilbene (PTE), a natural dimethylated resveratrol analog from blueberries, is known to have diverse pharmacological activities, including anticancer properties. In this study, we investigated the anticancer activity of PTE against human esophageal cancer cells both in vitro and in vivo and explored the role of endoplasmic reticulum (ER) stress (ERS) signaling in this process.

METHODS:

Cell viability, the apoptotic index, Caspase 3 activity, adhesion, migration, reactive oxygen species (ROS) levels, and glutathione (GSH) levels were detected to explore the effect of PTE on human EC109 esophageal cancer cells. Furthermore, siRNA transfection and a chemical inhibitor were employed to confirm the role of ERS.

RESULTS:

PTE treatment dose- and time-dependently decreased the viability of human esophageal cancer EC109 cells. PTE also decreased tumor cell adhesion, migration and intracellular GSH levels while increasing the apoptotic index, Caspase 3 activity and ROS levels, which suggest the strong anticancer activity of PTE. Furthermore, PTE treatment increased the expression of ERS-related molecules (GRP78, ATF6, p-PERK, p-eIF2α and CHOP), upregulated the pro-apoptosis-related protein PUMA and downregulated the anti-apoptosis-related protein Bcl-2 while promoting the translocation of cytochrome c from mitochondria to cytosol and the activation of Caspase 9 and Caspase 12. The downregulation of ERS signaling by CHOP siRNA desensitized esophageal cancer cells to PTE treatment, whereas upregulation of ERS signaling by thapsigargin (THA) had the opposite effect. N-Acetylcysteine (NAC), a ROS scavenger, also desensitized esophageal cancer cells to PTE treatment.

CONCLUSIONS:

Overall, the results indicate that PTE is a potent anti-cancer pharmaceutical against human esophageal cancer, and the possible mechanism involves the activation of ERS signaling pathways.

• Authors: Yingtong Feng, Yang Yang, Chongxi Fan, Shouyin Di, Wei Hu, Shuai Jiang, Tian Li, Zhiqiang Ma, Deng Chao, Xiao Feng, Zhenlong Xin, Sainan Pang, Xiaofei Li, Xiaolong Yan
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 38 Issue 3 Pg. 1226-44 ( 2016) ISSN: 1421-9778 [Electronic] Germany
• PMID: 26982591 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 S. Karger AG, Basel.

Chemical References

• Antineoplastic Agents
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Hspa5 protein, mouse
• Stilbenes
• pterostilbene

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (drug effects)
• Esophageal Neoplasms (drug therapy, metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Mice
• Signal Transduction (drug effects)
• Stilbenes (administration & dosage, pharmacology)
• Xenograft Model Antitumor Assays