Abstract:
:Esophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers in Japan. Anticancer chemotherapy has been useful for ESCC treatment. However, therapeutic options are limited. Recently, bisphosphonates (BPs), which are osteoporosis drugs, have shown anticancer effects in several cancer cell lines, but the effects against ESCC cell lines are unknown. In this study, we examined the cytotoxic effects of BPs and their mechanisms of cytotoxicity in human ESCC cell lines. A first-generation BP (etidronate), two second-generation BPs (alendronate and pamidronate), and two third-generation BPs (risedronate and zoledronate) were used in this study. All BPs, except etidronate, were cytotoxic, as indicated by increased caspase-3/7 activity and numbers of Annexin-fluorescein isothiocyanate positive cells in ESCC cell lines. From cell cycle analysis, G0/G1-phase arrest was observed upon treatment with second- and third-generation BPs. In addition, Cyclin D1 protein expression levels were decreased by second- and third-generation BP treatment. Although squalene and trans, trans-farnesol minimally affected BP cytotoxicity, treatment with geranylgeraniol inhibited BP cytotoxicity almost completely. We concluded that second- and third-generation BPs are cytotoxic to ESCC cell lines as they induce apoptosis and inhibit the cell cycle through mevalonate pathway inhibition. Therefore, BP treatment may be a beneficial therapy in ESCC patients.
journal_name
Dis Esophagusjournal_title
Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagusauthors
Minegaki T,Fukushima S,Morioka C,Takanashi H,Uno J,Tsuji S,Yamamoto S,Watanabe A,Tsujimoto M,Nishiguchi Kdoi
10.1111/dote.12370subject
Has Abstractpub_date
2016-08-01 00:00:00pages
656-62issue
6eissn
1120-8694issn
1442-2050journal_volume
29pub_type
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journal_title:Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus
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journal_title:Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus
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journal_title:Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus
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journal_title:Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
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journal_title:Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus
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