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Vol 88, No 6 (2017)
Research paper
Published online: 2017-06-30
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Potentialization of N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) cytotoxic activity by 2-(1-adamantylamino)-6-methylpyridine (AdAMP) in human ovarian cancer cells

Jacek Sieńko1, Witold Lasek2, Justyna Teliga-Czajkowska3, Roman Smolarczyk4, Krzysztof Czajkowski5
DOI: 10.5603/GP.a2017.0064
·
Pubmed: 28727129
·
Ginekol Pol 2017;88(6):307-311.
Affiliations
  1. 2nd Department of Obstetrics and Gynecology, Medical University of Warsaw, Poland, Poland
  2. Department of Immunology, Centre for Biostructure Research, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland
  3. Department of Obstetrics and Gynecology Didactics, Medical University of Warsaw, Warsaw, Poland
  4. Department of Gynecological Endocrinology, Medical University of Warsaw, Karowa 2, 00-315 Warsaw, Poland
  5. 2nd Department of Obstetrics and Gynecology, Medical University of Warsaw, Poland

open access

Vol 88, No 6 (2017)
ORIGINAL PAPERS Gynecology
Published online: 2017-06-30

Abstract

Objectives: TNF is one of the key cytokines involved in cancer development. TNF signaling can result in both stimulating and inhibitory signals that can result in opposite biological effects in cancerogenesis. 2-(1-adamantylamino)-6-methylpyridine (AdAMP) enhances TNF secretion whereas N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) is a NF-κB inhibitor potentially stimulating proapoptotic TNF signals. The aim of the study was to assess the effect of TPCK in combination with AdAMP on human ovarian cells.

Material and methods: CAOV-1 human ovarian cell line was incubated with TPCK and AdAMP for 24 hours. The cytotoxic effect was evaluated in a crystal violet assay. A monoclonal antibody against TNF, Infliximab, was added to examine the possible mechanism of interactions.

Results: Depending on concentration, AdAMP potentialized cytotoxic activity of TPCK or had a synergistic effect with TPCK. Infliximab did not reverse cytotoxicity of AdAMP and TPCK and in some cytotoxic and non-cytotoxic concentrations even enhanced their cytotoxicity.

Conclusions: AdAMP and TPCK cytotoxicity seems to be dependent on TNF signaling, however, the exact mechanism of interactions remains unclear.

Abstract

Objectives: TNF is one of the key cytokines involved in cancer development. TNF signaling can result in both stimulating and inhibitory signals that can result in opposite biological effects in cancerogenesis. 2-(1-adamantylamino)-6-methylpyridine (AdAMP) enhances TNF secretion whereas N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) is a NF-κB inhibitor potentially stimulating proapoptotic TNF signals. The aim of the study was to assess the effect of TPCK in combination with AdAMP on human ovarian cells.

Material and methods: CAOV-1 human ovarian cell line was incubated with TPCK and AdAMP for 24 hours. The cytotoxic effect was evaluated in a crystal violet assay. A monoclonal antibody against TNF, Infliximab, was added to examine the possible mechanism of interactions.

Results: Depending on concentration, AdAMP potentialized cytotoxic activity of TPCK or had a synergistic effect with TPCK. Infliximab did not reverse cytotoxicity of AdAMP and TPCK and in some cytotoxic and non-cytotoxic concentrations even enhanced their cytotoxicity.

Conclusions: AdAMP and TPCK cytotoxicity seems to be dependent on TNF signaling, however, the exact mechanism of interactions remains unclear.

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Keywords

AdAMP, TPCK, TNF, NF-kB inhibitors, proteasome, ovarian cancer, cell line

About this article
Title

Potentialization of N-a-tosyl-L-phenylalanine chloromethyl ketone (TPCK) cytotoxic activity by 2-(1-adamantylamino)-6-methylpyridine (AdAMP) in human ovarian cancer cells

Journal

Ginekologia Polska

Issue

Vol 88, No 6 (2017)

Article type

Research paper

Pages

307-311

Published online

2017-06-30

Page views

1261

Article views/downloads

1409

DOI

10.5603/GP.a2017.0064

Pubmed

28727129

Bibliographic record

Ginekol Pol 2017;88(6):307-311.

Keywords

AdAMP
TPCK
TNF
NF-kB inhibitors
proteasome
ovarian cancer
cell line

Authors

Jacek Sieńko
Witold Lasek
Justyna Teliga-Czajkowska
Roman Smolarczyk
Krzysztof Czajkowski

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