The anti-cancer effect of Ant-44 (Spermidine-Anthracene Conjugate) via Ornithine decarboxylase activity in K562 cells

Background Many tumors undergo dysregulation of polyamine homeostasis and up-regulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. The polyamine conjugate has shown promising chemopreventive activity against a range of human tumor cell types, but little is known ab...

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Main Authors: Abdul Ghani, Radiah, Phanstiel, Otto, Wallace, Heather M.
Format: Conference or Workshop Item
Language:English
Published: 2015
Subjects:
Online Access:http://irep.iium.edu.my/44493/
http://irep.iium.edu.my/44493/
http://irep.iium.edu.my/44493/1/44493.pdf
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spelling iium-444932018-01-03T01:01:10Z http://irep.iium.edu.my/44493/ The anti-cancer effect of Ant-44 (Spermidine-Anthracene Conjugate) via Ornithine decarboxylase activity in K562 cells Abdul Ghani, Radiah Phanstiel, Otto Wallace, Heather M. RB Pathology Background Many tumors undergo dysregulation of polyamine homeostasis and up-regulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. The polyamine conjugate has shown promising chemopreventive activity against a range of human tumor cell types, but little is known about the effect of this agent on leukemic cell lines. Here, we investigated whether inhibition of ODC by one of the polyamine anthracene conjugate, Ant 44, could contribute to the anti-cancer effect in human chronic myeloid leukaemic cells, K562. Methods Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results It has been shown that Ant-44 caused a decreased in ODC activity in a time-dependent manner. In K562 cells, a treatment with Ant-44 caused a decrease in intracellular spermine and putrescine levels which contribute to the decreased in total polyamine concentration. In contrast, the spermine level is increased with the treatment of Ant-44. Conclusion In conclusion, Ant-44 decreased ODC activity in the K562, and consequent decrease in putrescine and spermidine levels. However, perturbation of polyamine homeostasis leading to increases in intracellular spermine levels may contribute to a cytotoxic effect of the agent. The exact mechanism has not yet been elucidated, and the relevance of this observation to future chemopreventive strategies involving Ant-44 remains to be determined. 2015 Conference or Workshop Item NonPeerReviewed application/pdf en http://irep.iium.edu.my/44493/1/44493.pdf Abdul Ghani, Radiah and Phanstiel, Otto and Wallace, Heather M. (2015) The anti-cancer effect of Ant-44 (Spermidine-Anthracene Conjugate) via Ornithine decarboxylase activity in K562 cells. In: International Conference on Antioxidants and Degenerative Diseases (ICADD), 3rd-4th June 2015, Istana Hotel, Kuala Lumpur. (Unpublished) http://icadd.org.my/index.php
repository_type Digital Repository
institution_category Local University
institution International Islamic University Malaysia
building IIUM Repository
collection Online Access
language English
topic RB Pathology
spellingShingle RB Pathology
Abdul Ghani, Radiah
Phanstiel, Otto
Wallace, Heather M.
The anti-cancer effect of Ant-44 (Spermidine-Anthracene Conjugate) via Ornithine decarboxylase activity in K562 cells
description Background Many tumors undergo dysregulation of polyamine homeostasis and up-regulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. The polyamine conjugate has shown promising chemopreventive activity against a range of human tumor cell types, but little is known about the effect of this agent on leukemic cell lines. Here, we investigated whether inhibition of ODC by one of the polyamine anthracene conjugate, Ant 44, could contribute to the anti-cancer effect in human chronic myeloid leukaemic cells, K562. Methods Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results It has been shown that Ant-44 caused a decreased in ODC activity in a time-dependent manner. In K562 cells, a treatment with Ant-44 caused a decrease in intracellular spermine and putrescine levels which contribute to the decreased in total polyamine concentration. In contrast, the spermine level is increased with the treatment of Ant-44. Conclusion In conclusion, Ant-44 decreased ODC activity in the K562, and consequent decrease in putrescine and spermidine levels. However, perturbation of polyamine homeostasis leading to increases in intracellular spermine levels may contribute to a cytotoxic effect of the agent. The exact mechanism has not yet been elucidated, and the relevance of this observation to future chemopreventive strategies involving Ant-44 remains to be determined.
format Conference or Workshop Item
author Abdul Ghani, Radiah
Phanstiel, Otto
Wallace, Heather M.
author_facet Abdul Ghani, Radiah
Phanstiel, Otto
Wallace, Heather M.
author_sort Abdul Ghani, Radiah
title The anti-cancer effect of Ant-44 (Spermidine-Anthracene Conjugate) via Ornithine decarboxylase activity in K562 cells
title_short The anti-cancer effect of Ant-44 (Spermidine-Anthracene Conjugate) via Ornithine decarboxylase activity in K562 cells
title_full The anti-cancer effect of Ant-44 (Spermidine-Anthracene Conjugate) via Ornithine decarboxylase activity in K562 cells
title_fullStr The anti-cancer effect of Ant-44 (Spermidine-Anthracene Conjugate) via Ornithine decarboxylase activity in K562 cells
title_full_unstemmed The anti-cancer effect of Ant-44 (Spermidine-Anthracene Conjugate) via Ornithine decarboxylase activity in K562 cells
title_sort anti-cancer effect of ant-44 (spermidine-anthracene conjugate) via ornithine decarboxylase activity in k562 cells
publishDate 2015
url http://irep.iium.edu.my/44493/
http://irep.iium.edu.my/44493/
http://irep.iium.edu.my/44493/1/44493.pdf
first_indexed 2023-09-18T21:03:16Z
last_indexed 2023-09-18T21:03:16Z
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