Zoledronic acid, a third-generation bisphosphonate, inhibits cellular growth and induces apoptosis in oral carcinoma cell lines

Tamura,Takayuki; Shomori,Kohei; Nakabayashi,Motoki; Fujii,Nobuyuki; Ryoke,Kazuo; Ito,Hisao

doi:10.3892/or.2011.1152

April 2011 Volume 25 Issue 4

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April 2011 Volume 25 Issue 4

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Article

Zoledronic acid, a third-generation bisphosphonate, inhibits cellular growth and induces apoptosis in oral carcinoma cell lines

Authors:
- Takayuki Tamura
- Kohei Shomori
- Motoki Nakabayashi
- Nobuyuki Fujii
- Kazuo Ryoke
- Hisao Ito
View Affiliations / Copyright

Affiliations: Division of Organ Pathology, Department of Microbiology and Pathology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago, Tottori 683-8503, Japan
Pages: 1139-1143
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Published online on: January 18, 2011

https://doi.org/10.3892/or.2011.1152
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Abstract

Bisphosphonates (BPs) inhibit bone resorption by preventing osteoclast maturation and apoptosis induction. Recently, BPs have also been shown to have antitumor effects against various types of carcinomas in vitro and in vivo. In this study, we investigated the antitumor effect of zoledronic acid (ZOL), a third generation bisphosphonate, on proliferation, cell cycle and apoptosis of oral cancer cells. Direct antitumor effects of ZOL against four oral carcinoma cell lines (squamous cell carcinoma, HSC3, HSC4, SCCKN; salivary adenocarcinoma, HSY) were measured by WST assay. Apoptosis-related molecules were analyzed by Western blot analysis and cell cycle was analyzed by flow cytometry. ZOL had a dose-dependent antitumor effect in the four oral cancer cell lines. ZOL activated caspase-3, -8 and -9 and induced cellular apoptosis. Western blot analysis showed that ZOL increased cleaved anti-human poly(ADP-ribose) polymerase expression and decreased Bcl-2 and Bid expression. Treatment with ZOL increased the number of cells in apoptosis, sub G1 phase and S phase, and reduced the number of cells in the G0/G1 and G2/M phase in a concentration-dependent manner. ZOL inhibits cell proliferation and induces apoptosis of oral cancer cells in vitro. These findings suggest that ZOL might be beneficial in the treatment of oral carcinoma patients.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Zoledronic acid, a third-generation bisphosphonate, inhibits cellular growth and induces apoptosis in oral carcinoma cell lines

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Abstract

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