Cytotoxic activity of a polyamine analogue, monoaziridinylputrescine, against the PC-3 human prostatic carcinoma cell line Journal Article
| Authors: | Heston, W. D. W.; Yang, C. R.; Pliner, L.; Russo, P.; Covey, D. F. |
| Article Title: | Cytotoxic activity of a polyamine analogue, monoaziridinylputrescine, against the PC-3 human prostatic carcinoma cell line |
| Abstract: | We have previously demonstrated that prostate and prostate-derived rodent tumors can be manipulated into increasing their accumulation of radiolabeled putrescine by a-difluoromethylornithine (DFMO)-induced depletion of intracellular putrescine and spermidine. As methods which increase intracellular accumulation of cytotoxic agents often increase the chemotherapeutic effectiveness of the agent, we examined whether an alkylating derivative of putrescine would be cytotoxic to tumor cells. We present here our findings on the cytotoxicity of the aziridinyl derivative of putrescine (AZP) against prostatic cancer cells. The apparent Kmfor putrescine was 2.5 μmwith or without DFMO pretreatment and the apparent K1for AZP was 1 μmwith or without DFMO pretreatment. Intracellular polyamine depletion by DFMO pretreatment resulted in a 3.7-fold greater accumulation of AZP compared to non-DFMO-treated cells. The growth inhibitory activity of AZP was increased with prior polyamine depletion by DFMO with the 50% effective dose decreasing from 18 μmto 2.1 μm.Putrescine was able to block the cytotoxic effect of AZP. Putrescine was also able to rescue the AZP-treated PC-3 cells for up to 6 h following a 1-h exposure to AZP. It appears that aziridinylputrescine behaves like putrescine in that it competes with putrescine for uptake into the cell and, like putrescine, has its uptake into the cell increased by prior polyamine depletion. It differs from putrescine in that it expresses cytotoxic activity and inhibits the growth of the human prostate-derived PC-3 cell line. This cytotoxic activity is also increased by prior polyamine depletion. The cytotoxic behavior of AZP is dependent both on the concentration and duration of exposure. Putrescine can rescue the cells from the effect of AZP. AZP is a potentially useful cytotoxic analogue that utilizes the polyamine transport system for its uptake into the cell. © 1987, American Association for Cancer Research. All rights reserved. |
| Keywords: | unclassified drug; human cell; drug efficacy; cell survival; cell line; cytotoxicity; prostatic neoplasms; kinetics; eflornithine; tumor cell; drug cytotoxicity; prostate carcinoma; mathematics; intoxication; male genital system; putrescine; humans; human; male; priority journal; article; aziridinylputrescine |
| Journal Title: | Cancer Research |
| Volume: | 47 |
| Issue: | 14 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1987-07-15 |
| Start Page: | 3627 |
| End Page: | 3631 |
| Language: | English |
| PUBMED: | 3109728 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 February 2021 -- Source: Scopus |
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