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

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 microM 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.

• Authors: Ryuichiro Koshimune, Motoi Aoe, Shinichi Toyooka, Fumikata Hara, Mamoru Ouchida, Masaki Tokumo, Yoshifumi Sano, Hiroshi Date, Nobuyoshi Shimizu
• Journal: BMC cancer (BMC Cancer) Vol. 7 Pg. 8 (Jan 12 2007) ISSN: 1471-2407 [Electronic] England
• PMID: 17222343 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Diphosphonates
• Imidazoles
• YM 529

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Diphosphonates (pharmacology)
• Dose-Response Relationship, Drug
• Humans
• Imidazoles (pharmacology)
• Lung Neoplasms (drug therapy, pathology)