Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines

<p>Abstract</p> <p>Background</p> <p>YM529 is a newly developed nitrogen-containing bisphosphonate (BP) classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore e...

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Main Authors: Date Hiroshi, Sano Yoshifumi, Tokumo Masaki, Ouchida Mamoru, Hara Fumikata, Toyooka Shinichi, Aoe Motoi, Koshimune Ryuichiro, Shimizu Nobuyoshi
Format: Article
Language:English
Published: BMC 2007-01-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/7/8
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author Date Hiroshi
Sano Yoshifumi
Tokumo Masaki
Ouchida Mamoru
Hara Fumikata
Toyooka Shinichi
Aoe Motoi
Koshimune Ryuichiro
Shimizu Nobuyoshi
author_facet Date Hiroshi
Sano Yoshifumi
Tokumo Masaki
Ouchida Mamoru
Hara Fumikata
Toyooka Shinichi
Aoe Motoi
Koshimune Ryuichiro
Shimizu Nobuyoshi
author_sort Date Hiroshi
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>YM529 is a newly developed nitrogen-containing bisphosphonate (BP) classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both <it>in vitro </it>or/and <it>in vivo</it>. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157) were measured by MTS assay and calculated inhibition concentration 50 % (IC<sub>50</sub>) values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G<sub>1 </sub>method). We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis.</p> <p>Results</p> <p>We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC<sub>50 </sub>values were 2.1 to 7.9 μM and YM529 induced apoptosis and G<sub>1 </sub>arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819).</p> <p>Conclusion</p> <p>Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC.</p>
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spelling doaj.art-10c0e4dd9c5a4bbcbe4906d485e1fd302022-12-21T18:27:33ZengBMCBMC Cancer1471-24072007-01-0171810.1186/1471-2407-7-8Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell linesDate HiroshiSano YoshifumiTokumo MasakiOuchida MamoruHara FumikataToyooka ShinichiAoe MotoiKoshimune RyuichiroShimizu Nobuyoshi<p>Abstract</p> <p>Background</p> <p>YM529 is a newly developed nitrogen-containing bisphosphonate (BP) classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both <it>in vitro </it>or/and <it>in vivo</it>. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157) were measured by MTS assay and calculated inhibition concentration 50 % (IC<sub>50</sub>) values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G<sub>1 </sub>method). We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis.</p> <p>Results</p> <p>We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC<sub>50 </sub>values were 2.1 to 7.9 μM and YM529 induced apoptosis and G<sub>1 </sub>arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819).</p> <p>Conclusion</p> <p>Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC.</p>http://www.biomedcentral.com/1471-2407/7/8
spellingShingle Date Hiroshi
Sano Yoshifumi
Tokumo Masaki
Ouchida Mamoru
Hara Fumikata
Toyooka Shinichi
Aoe Motoi
Koshimune Ryuichiro
Shimizu Nobuyoshi
Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines
BMC Cancer
title Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines
title_full Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines
title_fullStr Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines
title_full_unstemmed Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines
title_short Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines
title_sort anti tumor effect of bisphosphonate ym529 on non small cell lung cancer cell lines
url http://www.biomedcentral.com/1471-2407/7/8
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