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

Ryuichiro Koshimune, Motoi Aoe, Shinichi Toyooka, Fumikata Hara, Mamoru Oouchida, Masaki Tokumo, Yoshifumi Sano, Hiroshi Date, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

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Abstract

Background: 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 in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC). Methods: 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 % (IC50) values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G1 method). We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis. Results: We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC50 values were 2.1 to 7.9 μM and YM529 induced apoptosis and G1 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). Conclusion: 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.

Original languageEnglish
Article number8
JournalBMC Cancer
Volume7
DOIs
Publication statusPublished - 2007

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Diphosphonates
Non-Small Cell Lung Carcinoma
Cell Line
Neoplasms
pamidronate
Apoptosis
YM 529
Adenosquamous Carcinoma
G1 Phase Cell Cycle Checkpoints
Mevalonic Acid
Agar Gel Electrophoresis
Hypercalcemia
DNA Fragmentation
Bone Resorption
Osteoporosis
Squamous Cell Carcinoma
Adenocarcinoma
Nitrogen
Down-Regulation
Western Blotting

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines. / Koshimune, Ryuichiro; Aoe, Motoi; Toyooka, Shinichi; Hara, Fumikata; Oouchida, Mamoru; Tokumo, Masaki; Sano, Yoshifumi; Date, Hiroshi; Shimizu, Nobuyoshi.

In: BMC Cancer, Vol. 7, 8, 2007.

Research output: Contribution to journalArticle

Koshimune, Ryuichiro ; Aoe, Motoi ; Toyooka, Shinichi ; Hara, Fumikata ; Oouchida, Mamoru ; Tokumo, Masaki ; Sano, Yoshifumi ; Date, Hiroshi ; Shimizu, Nobuyoshi. / Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell lines. In: BMC Cancer. 2007 ; Vol. 7.
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AU - Koshimune, Ryuichiro

AU - Aoe, Motoi

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AU - Hara, Fumikata

AU - Oouchida, Mamoru

AU - Tokumo, Masaki

AU - Sano, Yoshifumi

AU - Date, Hiroshi

AU - Shimizu, Nobuyoshi

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