Silencing Prion Protein in HT29 Human Colorectal Cancer Cells Enhances Anticancer Response to Fucoidan.

Abstract

BACKGROUND:

The putative functions of the cellular prion protein (PrP(c)) are believed to be associated with cell signaling, differentiation, survival, and cancer progression. With respect to cancer development and progression, elevations and mutations of PrP(c) expression have been shown to increase the risk for malignancy and metastasis in breast and colorectal cancer. Since both natural supplements and direct regulation of PrP(c) expression contribute to inhibition of cancer progression and growth, we hypothesized that knockdown of PrP(c) could lead to an enhanced synergic effect on the inhibition of cancer growth by fucoidan.

MATERIALS AND METHODS:

PrP(c) expression was suppressed in HT29 human colon cancer cells by utilizing small-interfering RNA (si-PRNP), and cells were subsequently used to study the antiproliferative and anticancer effects of fucoidan treatment of HT29 human colon cancer cells.

RESULTS:

Fucoidan treatment significantly inhibited growth and reduced cyclin and cyclin-dependent kinase (CDK) expression in HT29 colon cancer cells. Furthermore, silencing PrP(c) expression with si-PRNP amplified the fucoidan-induced changes in cell proliferation, apoptosis, and migration. Intraperitoneal injection of si-PRNP with fucoidan reduced proliferation and tumor volume in Balb/c nude mice. This enhanced antitumor efficacy was associated with decreased angiogenesis.

CONCLUSION:

Combination of fucoidan with silencing of PrP(c) has a synergic effect on the inhibition of HT29 colon cancer cell growth. Furthermore, we provide evidence for the therapeutic application of PrP(c) silencing with other anticancer drugs for cancer.

• Authors: Chul Won Yun, Seungpil Yun, Jun Hee Lee, Yong-Seok Han, Yeo Min Yoon, Daniel An, Sang Hun Lee
• Journal: Anticancer research (Anticancer Res) Vol. 36 Issue 9 Pg. 4449-58 (09 2016) ISSN: 1791-7530 [Electronic] Greece
• PMID: 27630281 (Publication Type: Journal Article)
• Copyright: Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Platelet Endothelial Cell Adhesion Molecule-1
• Polysaccharides
• Prion Proteins
• Proliferating Cell Nuclear Antigen
• RNA, Small Interfering
• Vascular Endothelial Growth Factor A
• fucoidan
• Caspase 3

Topics

• Animals
• Antineoplastic Agents (chemistry)
• Apoptosis
• Caspase 3 (metabolism)
• Cell Cycle
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Colonic Neoplasms (drug therapy)
• Gene Silencing
• HT29 Cells
• Humans
• Immunohistochemistry
• Male
• Mice
• Mice, Inbred BALB C
• Platelet Endothelial Cell Adhesion Molecule-1 (chemistry)
• Polysaccharides (chemistry)
• Prion Proteins (genetics, metabolism)
• Proliferating Cell Nuclear Antigen (metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)