Inhibition of cholangiocarcinoma growth by tannic acid

Carla Marienfeld, Laura Tadlock, Yoko Yamagiwa, Tushar C Patel

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Cholangiocarcinoma is an aggressive malignancy of the biliary tract for which effective treatment is lacking. Tannic acid (TA) is a naturally occurring polyphenolic compound with antioxidant and radical scavenging properties as well as anticarcinogenic effects. TA inhibited proliferation of malignant human cholangiocytes in vitro. Furthermore, the growth rate of Mz-ChA-1 cholangiocarcinoma xenografts in balb/c athymic mice was reduced from 10.9 ± 1.8 mm3/d in mice fed with normal water to 5.5 ± 1.2 mm3/d in mice fed with water containing 0.05% TA. Pretreatment with 50 μg/mL TA for 24 hours before xenograft implantation increased tumor latency by 2.5-fold compared with untreated controls, and decreased subsequent growth rates compared with controls in the absence of TA feeding. TA was not cytotoxic to Mz-ChA-1 cells in vitro, but enhanced sensitivity to camptothecin cytotoxicity. TA potently inhibited cell cycle progression, and increased expression of the cyclin-dependent kinase inhibitor p27KIP1. In addition, TA (0-50 μg/mL) inhibited proteasomal activity in cholangiocyte cell extracts in a concentration-dependent manner. In conclusion, the growth inhibitory effects of TA may result from dysregulation of cell cycle progression due to altered proteasomal degradation of these cell cycle regulatory proteins. TA warrants evaluation as a candidate for the treatment of human cholangiocarcinoma either by itself or in combination with other chemotherapeutic agents.

Original languageEnglish (US)
Pages (from-to)1097-1104
Number of pages8
JournalHepatology
Volume37
Issue number5
DOIs
StatePublished - May 1 2003
Externally publishedYes

Fingerprint

Cholangiocarcinoma
Tannins
Growth
Heterografts
Cell Cycle
Anticarcinogenic Agents
Camptothecin
Cell Cycle Proteins
Cyclin-Dependent Kinases
Water
Biliary Tract
Cell Extracts
Nude Mice
Neoplasms
Antioxidants

ASJC Scopus subject areas

  • Hepatology

Cite this

Inhibition of cholangiocarcinoma growth by tannic acid. / Marienfeld, Carla; Tadlock, Laura; Yamagiwa, Yoko; Patel, Tushar C.

In: Hepatology, Vol. 37, No. 5, 01.05.2003, p. 1097-1104.

Research output: Contribution to journalArticle

Marienfeld, C, Tadlock, L, Yamagiwa, Y & Patel, TC 2003, 'Inhibition of cholangiocarcinoma growth by tannic acid', Hepatology, vol. 37, no. 5, pp. 1097-1104. https://doi.org/10.1053/jhep.2003.50192
Marienfeld, Carla ; Tadlock, Laura ; Yamagiwa, Yoko ; Patel, Tushar C. / Inhibition of cholangiocarcinoma growth by tannic acid. In: Hepatology. 2003 ; Vol. 37, No. 5. pp. 1097-1104.
@article{796602c51cec4f2bba9694bea092c75f,
title = "Inhibition of cholangiocarcinoma growth by tannic acid",
abstract = "Cholangiocarcinoma is an aggressive malignancy of the biliary tract for which effective treatment is lacking. Tannic acid (TA) is a naturally occurring polyphenolic compound with antioxidant and radical scavenging properties as well as anticarcinogenic effects. TA inhibited proliferation of malignant human cholangiocytes in vitro. Furthermore, the growth rate of Mz-ChA-1 cholangiocarcinoma xenografts in balb/c athymic mice was reduced from 10.9 ± 1.8 mm3/d in mice fed with normal water to 5.5 ± 1.2 mm3/d in mice fed with water containing 0.05{\%} TA. Pretreatment with 50 μg/mL TA for 24 hours before xenograft implantation increased tumor latency by 2.5-fold compared with untreated controls, and decreased subsequent growth rates compared with controls in the absence of TA feeding. TA was not cytotoxic to Mz-ChA-1 cells in vitro, but enhanced sensitivity to camptothecin cytotoxicity. TA potently inhibited cell cycle progression, and increased expression of the cyclin-dependent kinase inhibitor p27KIP1. In addition, TA (0-50 μg/mL) inhibited proteasomal activity in cholangiocyte cell extracts in a concentration-dependent manner. In conclusion, the growth inhibitory effects of TA may result from dysregulation of cell cycle progression due to altered proteasomal degradation of these cell cycle regulatory proteins. TA warrants evaluation as a candidate for the treatment of human cholangiocarcinoma either by itself or in combination with other chemotherapeutic agents.",
author = "Carla Marienfeld and Laura Tadlock and Yoko Yamagiwa and Patel, {Tushar C}",
year = "2003",
month = "5",
day = "1",
doi = "10.1053/jhep.2003.50192",
language = "English (US)",
volume = "37",
pages = "1097--1104",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

TY - JOUR

T1 - Inhibition of cholangiocarcinoma growth by tannic acid

AU - Marienfeld, Carla

AU - Tadlock, Laura

AU - Yamagiwa, Yoko

AU - Patel, Tushar C

PY - 2003/5/1

Y1 - 2003/5/1

N2 - Cholangiocarcinoma is an aggressive malignancy of the biliary tract for which effective treatment is lacking. Tannic acid (TA) is a naturally occurring polyphenolic compound with antioxidant and radical scavenging properties as well as anticarcinogenic effects. TA inhibited proliferation of malignant human cholangiocytes in vitro. Furthermore, the growth rate of Mz-ChA-1 cholangiocarcinoma xenografts in balb/c athymic mice was reduced from 10.9 ± 1.8 mm3/d in mice fed with normal water to 5.5 ± 1.2 mm3/d in mice fed with water containing 0.05% TA. Pretreatment with 50 μg/mL TA for 24 hours before xenograft implantation increased tumor latency by 2.5-fold compared with untreated controls, and decreased subsequent growth rates compared with controls in the absence of TA feeding. TA was not cytotoxic to Mz-ChA-1 cells in vitro, but enhanced sensitivity to camptothecin cytotoxicity. TA potently inhibited cell cycle progression, and increased expression of the cyclin-dependent kinase inhibitor p27KIP1. In addition, TA (0-50 μg/mL) inhibited proteasomal activity in cholangiocyte cell extracts in a concentration-dependent manner. In conclusion, the growth inhibitory effects of TA may result from dysregulation of cell cycle progression due to altered proteasomal degradation of these cell cycle regulatory proteins. TA warrants evaluation as a candidate for the treatment of human cholangiocarcinoma either by itself or in combination with other chemotherapeutic agents.

AB - Cholangiocarcinoma is an aggressive malignancy of the biliary tract for which effective treatment is lacking. Tannic acid (TA) is a naturally occurring polyphenolic compound with antioxidant and radical scavenging properties as well as anticarcinogenic effects. TA inhibited proliferation of malignant human cholangiocytes in vitro. Furthermore, the growth rate of Mz-ChA-1 cholangiocarcinoma xenografts in balb/c athymic mice was reduced from 10.9 ± 1.8 mm3/d in mice fed with normal water to 5.5 ± 1.2 mm3/d in mice fed with water containing 0.05% TA. Pretreatment with 50 μg/mL TA for 24 hours before xenograft implantation increased tumor latency by 2.5-fold compared with untreated controls, and decreased subsequent growth rates compared with controls in the absence of TA feeding. TA was not cytotoxic to Mz-ChA-1 cells in vitro, but enhanced sensitivity to camptothecin cytotoxicity. TA potently inhibited cell cycle progression, and increased expression of the cyclin-dependent kinase inhibitor p27KIP1. In addition, TA (0-50 μg/mL) inhibited proteasomal activity in cholangiocyte cell extracts in a concentration-dependent manner. In conclusion, the growth inhibitory effects of TA may result from dysregulation of cell cycle progression due to altered proteasomal degradation of these cell cycle regulatory proteins. TA warrants evaluation as a candidate for the treatment of human cholangiocarcinoma either by itself or in combination with other chemotherapeutic agents.

UR - http://www.scopus.com/inward/record.url?scp=0037698800&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037698800&partnerID=8YFLogxK

U2 - 10.1053/jhep.2003.50192

DO - 10.1053/jhep.2003.50192

M3 - Article

C2 - 12717390

AN - SCOPUS:0037698800

VL - 37

SP - 1097

EP - 1104

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 5

ER -