Sodium taurocholate cotransporting polypeptide mediates dual actions of deoxycholic acid in human hepatocellular carcinoma cells: Enhanced apoptosis versus growth stimulation

Eun Sun Jang, Jung-Hwan Yoon, Sung Hee Lee, Soo Mi Lee, Jeong-Hoon Lee, Su Jong Yu, Yoon Jun Kim, Hyo Suk Lee, Chung Yong Kim

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6 Citations (Scopus)

Abstract

Purpose: The hydrophobic bile acid, deoxycholic acid (DC), can induce apoptosis in hepatocytes. The roles of DC and its transporter are not yet established in hepatocellular carcinoma (HCC) cells. We investigated DC-induced alterations in HCC cell growth, with a particular focus on the effect of the expression of bile acid (BA)-transporting Na+-dependent taurocholic cotransporting polypeptides (NTCPs). Methods: We determined NTCP expression in four human HCC cell lines: Huh-BAT, Huh-7, SNU-761, and SNU-475. NTCP expression and apoptotic signaling cascades were examined by immunoblot analyses. Cell viability was assessed using the 3,4-(5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt assay. Wound healing and invasion assays were performed to evaluate cell migration and invasion abilities. Real-time polymerase chain reaction was performed to measure IL-8 expression levels. Nuclear factor kappa B (NF-κB) activity was evaluated by enzyme-linked immunosorbent assay. Results: The HCC cell lines revealed varying NTCP expression levels, and DC treatment had dual effects, depending on NTCP expression. DC induced apoptosis in NTCP-positive HCC cells, especially under hypoxic conditions. In NTCP-negative HCC cells, simultaneous treatment with DC and cyclooxygenase inhibitor markedly decreased aggressive cellular behaviors via the inhibition of NF-κB/COX-2/IL-8 pathways. Conclusion: Hydrophobic bile acid offers therapeutic potential for patients with advanced HCC via different mechanisms depending on NTCP expression levels within the tumor.

Original languageEnglish
Pages (from-to)133-144
Number of pages12
JournalJournal of Cancer Research and Clinical Oncology
Volume140
Issue number1
DOIs
StatePublished - 1 Jan 2014

Fingerprint

Deoxycholic Acid
Hepatocellular Carcinoma
Apoptosis
Peptides
Growth
Bile Acids and Salts
NF-kappa B
Interleukin-8
Tetrazolium Salts
Cell Line
Cyclooxygenase Inhibitors
sodium-bile acid cotransporter
Wound Healing
Cell Movement
Real-Time Polymerase Chain Reaction
Hepatocytes
Cell Survival
Therapeutics
Enzyme-Linked Immunosorbent Assay

Keywords

  • Apoptosis
  • Deoxycholic acid
  • Hepatocellular carcinoma
  • IL-8
  • NF-κB
  • Sodium taurocholate cotransporting polypeptide

Cite this

@article{11da15fd27114319b0728ce26d1c18ea,
title = "Sodium taurocholate cotransporting polypeptide mediates dual actions of deoxycholic acid in human hepatocellular carcinoma cells: Enhanced apoptosis versus growth stimulation",
abstract = "Purpose: The hydrophobic bile acid, deoxycholic acid (DC), can induce apoptosis in hepatocytes. The roles of DC and its transporter are not yet established in hepatocellular carcinoma (HCC) cells. We investigated DC-induced alterations in HCC cell growth, with a particular focus on the effect of the expression of bile acid (BA)-transporting Na+-dependent taurocholic cotransporting polypeptides (NTCPs). Methods: We determined NTCP expression in four human HCC cell lines: Huh-BAT, Huh-7, SNU-761, and SNU-475. NTCP expression and apoptotic signaling cascades were examined by immunoblot analyses. Cell viability was assessed using the 3,4-(5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt assay. Wound healing and invasion assays were performed to evaluate cell migration and invasion abilities. Real-time polymerase chain reaction was performed to measure IL-8 expression levels. Nuclear factor kappa B (NF-κB) activity was evaluated by enzyme-linked immunosorbent assay. Results: The HCC cell lines revealed varying NTCP expression levels, and DC treatment had dual effects, depending on NTCP expression. DC induced apoptosis in NTCP-positive HCC cells, especially under hypoxic conditions. In NTCP-negative HCC cells, simultaneous treatment with DC and cyclooxygenase inhibitor markedly decreased aggressive cellular behaviors via the inhibition of NF-κB/COX-2/IL-8 pathways. Conclusion: Hydrophobic bile acid offers therapeutic potential for patients with advanced HCC via different mechanisms depending on NTCP expression levels within the tumor.",
keywords = "Apoptosis, Deoxycholic acid, Hepatocellular carcinoma, IL-8, NF-κB, Sodium taurocholate cotransporting polypeptide",
author = "Jang, {Eun Sun} and Jung-Hwan Yoon and Lee, {Sung Hee} and Lee, {Soo Mi} and Jeong-Hoon Lee and Yu, {Su Jong} and Kim, {Yoon Jun} and Lee, {Hyo Suk} and Kim, {Chung Yong}",
year = "2014",
month = "1",
day = "1",
doi = "10.1007/s00432-013-1554-6",
language = "English",
volume = "140",
pages = "133--144",
journal = "Journal of cancer research and clinical oncology",
issn = "0171-5216",
publisher = "Springer Verlag",
number = "1",

}

TY - JOUR

T1 - Sodium taurocholate cotransporting polypeptide mediates dual actions of deoxycholic acid in human hepatocellular carcinoma cells

T2 - Enhanced apoptosis versus growth stimulation

AU - Jang, Eun Sun

AU - Yoon, Jung-Hwan

AU - Lee, Sung Hee

AU - Lee, Soo Mi

AU - Lee, Jeong-Hoon

AU - Yu, Su Jong

AU - Kim, Yoon Jun

AU - Lee, Hyo Suk

AU - Kim, Chung Yong

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Purpose: The hydrophobic bile acid, deoxycholic acid (DC), can induce apoptosis in hepatocytes. The roles of DC and its transporter are not yet established in hepatocellular carcinoma (HCC) cells. We investigated DC-induced alterations in HCC cell growth, with a particular focus on the effect of the expression of bile acid (BA)-transporting Na+-dependent taurocholic cotransporting polypeptides (NTCPs). Methods: We determined NTCP expression in four human HCC cell lines: Huh-BAT, Huh-7, SNU-761, and SNU-475. NTCP expression and apoptotic signaling cascades were examined by immunoblot analyses. Cell viability was assessed using the 3,4-(5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt assay. Wound healing and invasion assays were performed to evaluate cell migration and invasion abilities. Real-time polymerase chain reaction was performed to measure IL-8 expression levels. Nuclear factor kappa B (NF-κB) activity was evaluated by enzyme-linked immunosorbent assay. Results: The HCC cell lines revealed varying NTCP expression levels, and DC treatment had dual effects, depending on NTCP expression. DC induced apoptosis in NTCP-positive HCC cells, especially under hypoxic conditions. In NTCP-negative HCC cells, simultaneous treatment with DC and cyclooxygenase inhibitor markedly decreased aggressive cellular behaviors via the inhibition of NF-κB/COX-2/IL-8 pathways. Conclusion: Hydrophobic bile acid offers therapeutic potential for patients with advanced HCC via different mechanisms depending on NTCP expression levels within the tumor.

AB - Purpose: The hydrophobic bile acid, deoxycholic acid (DC), can induce apoptosis in hepatocytes. The roles of DC and its transporter are not yet established in hepatocellular carcinoma (HCC) cells. We investigated DC-induced alterations in HCC cell growth, with a particular focus on the effect of the expression of bile acid (BA)-transporting Na+-dependent taurocholic cotransporting polypeptides (NTCPs). Methods: We determined NTCP expression in four human HCC cell lines: Huh-BAT, Huh-7, SNU-761, and SNU-475. NTCP expression and apoptotic signaling cascades were examined by immunoblot analyses. Cell viability was assessed using the 3,4-(5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt assay. Wound healing and invasion assays were performed to evaluate cell migration and invasion abilities. Real-time polymerase chain reaction was performed to measure IL-8 expression levels. Nuclear factor kappa B (NF-κB) activity was evaluated by enzyme-linked immunosorbent assay. Results: The HCC cell lines revealed varying NTCP expression levels, and DC treatment had dual effects, depending on NTCP expression. DC induced apoptosis in NTCP-positive HCC cells, especially under hypoxic conditions. In NTCP-negative HCC cells, simultaneous treatment with DC and cyclooxygenase inhibitor markedly decreased aggressive cellular behaviors via the inhibition of NF-κB/COX-2/IL-8 pathways. Conclusion: Hydrophobic bile acid offers therapeutic potential for patients with advanced HCC via different mechanisms depending on NTCP expression levels within the tumor.

KW - Apoptosis

KW - Deoxycholic acid

KW - Hepatocellular carcinoma

KW - IL-8

KW - NF-κB

KW - Sodium taurocholate cotransporting polypeptide

UR - http://www.scopus.com/inward/record.url?scp=84892669356&partnerID=8YFLogxK

U2 - 10.1007/s00432-013-1554-6

DO - 10.1007/s00432-013-1554-6

M3 - Article

AN - SCOPUS:84892669356

VL - 140

SP - 133

EP - 144

JO - Journal of cancer research and clinical oncology

JF - Journal of cancer research and clinical oncology

SN - 0171-5216

IS - 1

ER -