Bufalin reduces the level of topoisomerase II in human leukemia cells and affects the cytotoxicity of anticancer drugs

When human leukemia HL-60 cells were treated with 10 −7 M bufalin, the amounts of both topoisomerase (topo) IIα and IIβ and the activity of topo II decreased markedly and were almost undetectable 18 h after the start of treatment. The level of topo II mRNA started to decrease immediately after the s...

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Veröffentlicht in:Leukemia research 1997-09, Vol.21 (9), p.875-883
Hauptverfasser: Hashimoto, Sachiko, Jing, Yongkui, Kawazoe, Nobuko, Masuda, Yutaka, Nakajo, Shigeo, Yoshida, Takemi, Kuroiwa, Yukio, Nakaya, Kazuyasu
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container_end_page 883
container_issue 9
container_start_page 875
container_title Leukemia research
container_volume 21
creator Hashimoto, Sachiko
Jing, Yongkui
Kawazoe, Nobuko
Masuda, Yutaka
Nakajo, Shigeo
Yoshida, Takemi
Kuroiwa, Yukio
Nakaya, Kazuyasu
description When human leukemia HL-60 cells were treated with 10 −7 M bufalin, the amounts of both topoisomerase (topo) IIα and IIβ and the activity of topo II decreased markedly and were almost undetectable 18 h after the start of treatment. The level of topo II mRNA started to decrease immediately after the start of treatment with bufalin, with a subsequent decrease in the amount of topo IIα protein. These changes preceded the fragmentation of DNA, a typical feature of apoptosis. The results suggest that bufalin caused a marked decrease in the steady-state level of topo IIα mRNA, which led to a decrease in the amount and activity of the enzyme and to the induction of apoptosis. A reduction in the level of topo IIα by bufalin was also observed in other lines of human leukemia cells such as ML1 and U937. The results were exploited to potentiate the effects of cisplatin and retinoic acid (RA) on HL-60 cells: pretreatment of HL-60 cells with 10 −7 M bufalin for 6 h increased the inhibitory effects of cisplatin and RA on cell growth and enhanced the induction of cell death.
doi_str_mv 10.1016/S0145-2126(97)00061-1
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Drug treatments</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Neoplasm - biosynthesis</topic><topic>Tetradecanoylphorbol Acetate - pharmacology</topic><topic>topoisomerase II</topic><topic>Topoisomerase II Inhibitors</topic><topic>Tretinoin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hashimoto, Sachiko</creatorcontrib><creatorcontrib>Jing, Yongkui</creatorcontrib><creatorcontrib>Kawazoe, Nobuko</creatorcontrib><creatorcontrib>Masuda, Yutaka</creatorcontrib><creatorcontrib>Nakajo, Shigeo</creatorcontrib><creatorcontrib>Yoshida, Takemi</creatorcontrib><creatorcontrib>Kuroiwa, Yukio</creatorcontrib><creatorcontrib>Nakaya, Kazuyasu</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Leukemia research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hashimoto, Sachiko</au><au>Jing, Yongkui</au><au>Kawazoe, Nobuko</au><au>Masuda, Yutaka</au><au>Nakajo, Shigeo</au><au>Yoshida, Takemi</au><au>Kuroiwa, Yukio</au><au>Nakaya, Kazuyasu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bufalin reduces the level of topoisomerase II in human leukemia cells and affects the cytotoxicity of anticancer drugs</atitle><jtitle>Leukemia research</jtitle><addtitle>Leuk Res</addtitle><date>1997-09-01</date><risdate>1997</risdate><volume>21</volume><issue>9</issue><spage>875</spage><epage>883</epage><pages>875-883</pages><issn>0145-2126</issn><eissn>1873-5835</eissn><coden>LEREDD</coden><abstract>When human leukemia HL-60 cells were treated with 10 −7 M bufalin, the amounts of both topoisomerase (topo) IIα and IIβ and the activity of topo II decreased markedly and were almost undetectable 18 h after the start of treatment. The level of topo II mRNA started to decrease immediately after the start of treatment with bufalin, with a subsequent decrease in the amount of topo IIα protein. These changes preceded the fragmentation of DNA, a typical feature of apoptosis. The results suggest that bufalin caused a marked decrease in the steady-state level of topo IIα mRNA, which led to a decrease in the amount and activity of the enzyme and to the induction of apoptosis. A reduction in the level of topo IIα by bufalin was also observed in other lines of human leukemia cells such as ML1 and U937. The results were exploited to potentiate the effects of cisplatin and retinoic acid (RA) on HL-60 cells: pretreatment of HL-60 cells with 10 −7 M bufalin for 6 h increased the inhibitory effects of cisplatin and RA on cell growth and enhanced the induction of cell death.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>9393603</pmid><doi>10.1016/S0145-2126(97)00061-1</doi><tpages>9</tpages></addata></record>
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subjects Antineoplastic agents
Antineoplastic Agents - pharmacology
apoptosis
Apoptosis - drug effects
Biological and medical sciences
Bufalin
Bufanolides - pharmacology
Cisplatin - pharmacology
DNA Fragmentation
DNA Topoisomerases, Type II - biosynthesis
DNA Topoisomerases, Type II - genetics
DNA, Neoplasm - analysis
Drug Synergism
Enzyme Induction - drug effects
Enzyme Inhibitors - pharmacology
General aspects
HL-60 Cells - drug effects
HL-60 Cells - enzymology
Humans
Isoenzymes - antagonists & inhibitors
Isoenzymes - biosynthesis
Isoenzymes - genetics
leukemia cell
Medical sciences
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
Pharmacology. Drug treatments
RNA, Messenger - biosynthesis
RNA, Neoplasm - biosynthesis
Tetradecanoylphorbol Acetate - pharmacology
topoisomerase II
Topoisomerase II Inhibitors
Tretinoin - pharmacology
title Bufalin reduces the level of topoisomerase II in human leukemia cells and affects the cytotoxicity of anticancer drugs
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