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

• Main Authors: Abdul Ghani, Radiah, Phanstiel, Otto, Wallace, Heather M.
• Format: Conference or Workshop Item
• Language: English
• Published: 2015
• Subjects: RB Pathology
• Online Access: http://irep.iium.edu.my/44493/1/44493.pdf; http://irep.iium.edu.my/44493/; http://icadd.org.my/index.php

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.