Cancer Chemoprevention Effects of Geldanamycin and 17-AAG in Human Oral Squamous Cell Carcinoma
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
HSP90 regulates various proteins involved in differentiation and cell survival. Levels of HSP90 tend to increase during development of squamous cell carcinoma in the head and neck including the mouth. Thus, many studies have been conducted to treat these cancers through suppression of HSP90. This study investigated the effect of two HSP90 inhibitors, geldanamycin and 17-AAG, on the proliferation, apoptosis, and invasion of human oral squamous cell carcinoma cells. Cell survival and cell cycle analyses, as well as western blot analysis, were performed with oral cancer cell lines, YD-10B and YD-38. After treatment with HSP90 inhibitors, cell proliferation was significantly inhibited. When YD-10B and YD-38 cells were treated with various concentrations of geldanamycin and 17-AAG (0, 0.1, 0.3, 1 and 10 M) for 24 hr, the growth of YD-10B cells was markedly reduced compared to that of YD-38 cells. Thereafter, the cells were subjected to flow cytometry, which revealed G2 arrest. These results demonstrated that geldanamycin induced G2 arrest and inhibited cell proliferation through the p-GSK-3 pathway in YD-10B and YD-38 cells, thus inhibiting cell survival. HSP90 inhibitors are therefore expected to have a therapeutic effect on various cancer cell lines.
Abstract
HSP90 regulates various proteins involved in differentiation and cell survival. Levels of HSP90 tend to increase during development of squamous cell carcinoma in the head and neck including the mouth. Thus, many studies have been conducted to treat these cancers through suppression of HSP90. This study investigated the effect of two HSP90 inhibitors, geldanamycin and 17-AAG, on the proliferation, apoptosis, and invasion of human oral squamous cell carcinoma cells. Cell survival and cell cycle analyses, as well as western blot analysis, were performed with oral cancer cell lines, YD-10B and YD-38. After treatment with HSP90 inhibitors, cell proliferation was significantly inhibited. When YD-10B and YD-38 cells were treated with various concentrations of geldanamycin and 17-AAG (0, 0.1, 0.3, 1 and 10 M) for 24 hr, the growth of YD-10B cells was markedly reduced compared to that of YD-38 cells. Thereafter, the cells were subjected to flow cytometry, which revealed G2 arrest. These results demonstrated that geldanamycin induced G2 arrest and inhibited cell proliferation through the p-GSK-3 pathway in YD-10B and YD-38 cells, thus inhibiting cell survival. HSP90 inhibitors are therefore expected to have a therapeutic effect on various cancer cell lines.
참고문헌 (28)
- K J Harrington, "Guidelines for preclinical and early phase clinical assessment of novel radiosensitisers", British Journal of Cancer, 105(5), pp.628~639 (2011), Springer Nature[DOI]
- Magnus T. Dillon, "Human Papillomavirus–Negative Pharyngeal Cancer", Journal of Clinical Oncology, 33(29), pp.3251~3261 (2015), American Society of Clinical Oncology (ASCO)[DOI]
- Jane Trepel, "Targeting the dynamic HSP90 complex in cancer", Nature Reviews Cancer, 10(8), pp.537~549 (2010), Springer Nature[DOI]
- Pearl LH, "Structure, function, and mechanism of the HSP90 molecular chaperone", Adv Protein Chem, 59, pp.157~186 (2001)[DOI]
- Luke Whitesell, "HSP90 and the chaperoning of cancer", Nature Reviews Cancer, 5(10), pp.761~772 (2005), Springer Nature[DOI]
- Neckers L, "haperoning oncogenes: HSP90 as a target of geldanamycin", Handb Exp Pharmacol, 172, pp.259~277 (2006)[DOI]
- Pacey S, "HSP90 inhibitors in the clinic", Handb Exp Pharmacol, 172, pp.331~358 (2006)[DOI]
- Theodor W. Schulte, "Disruption of the Raf-1-Hsp90 Molecular Complex Results in Destabilization of Raf-1 and Loss of Raf-1-Ras Association", Journal of Biological Chemistry, 270(41), pp.24585~24588 (1995), American Society for Biochemistry & Molecular Biology (ASBMB)[DOI]
- 이은주, "Characterization of newly established oral cancer cell lines derived fromsix squamous cell carcinoma and two mucoepidermoid carcinoma cells", Experimental and Molecular Medicine, 37(5), pp.379~390 (2005), 생화학분자생물학회
- Scott M. Lippman, "Molecular Markers of the Risk of Oral Cancer", New England Journal of Medicine, 344(17), pp.1323~1326 (2001), Massachusetts Medical Society[DOI]
- W. Xu, "Chaperone-dependent E3 ubiquitin ligase CHIP mediates a degradative pathway for c-ErbB2", Neu, 2002, pp.99(20), 12847~12852[DOI]
- Pengcheng Zhou, "ErbB2 Degradation Mediated by the Co-chaperone Protein CHIP", Journal of Biological Chemistry, 278(16), pp.13829~13837 (2003), American Society for Biochemistry & Molecular Biology (ASBMB)[DOI]
- H. Machida, "Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation", International Journal of Radiation Biology, 79(12), pp.973~980 (2009), Informa UK Limited[DOI]
- Miho Noguchi, "Inhibition of homologous recombination repair in irradiated tumor cells pretreated with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin", Biochemical and Biophysical Research Communications, 351(3), pp.658~663 (2006), Elsevier BV[DOI]
- SHINSUKE HASHIDA, "Hsp90 inhibitor NVP-AUY922 enhances the radiation sensitivity of lung cancer cell lines with acquired resistance to EGFR-tyrosine kinase inhibitors", Oncology Reports, 33(3), pp.1499~1504 (2015), Spandidos Publications[DOI]
- Young Eun Choi, "Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells", Oncotarget, 5(9), pp.2678~2687 (2014), Impact Journals, LLC[DOI]
- J-L Roh, "The Hsp90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin increases cisplatin antitumor activity by inducing p53-mediated apoptosis in head and neck cancer", Cell Death & Disease, 4(12), pp.e956~e956 (2013), Springer Nature[DOI]
- Soichiro Yoshida, "Low-dose Hsp90 inhibitors tumor-selectively sensitize bladder cancer cells to chemoradiotherapy", Cell Cycle, 10(24), pp.4291~4299 (2014), Informa UK Limited[DOI]
- H. E. Barker, "CHK1 Inhibition Radiosensitizes Head and Neck Cancers to Paclitaxel-Based Chemoradiotherapy", Molecular Cancer Therapeutics, 15(9), pp.2042~2054 (2016), American Association for Cancer Research (AACR)[DOI]
- Jay A. Friedman, "HSP90 Inhibitor SNX5422", 2112 Targets the Dysregulated Signal and Transcription Factor Network and Malignant Phenotype of Head and Neck Squamous Cell Carcinoma, 2013, pp.6(4), 429~441[DOI]
- Tanvi Suhane, "Both the Charged Linker Region and ATPase Domain of Hsp90 Are Essential for Rad51-Dependent DNA Repair", Eukaryotic Cell, 14(1), pp.64~77 (2014), American Society for Microbiology[DOI]
- Xiaoying Yin, "BIIB021, a novel HSP90 inhibitor, sensitizes head and neck squamous cell carcinoma to radiotherapy", International Journal of Cancer, 126, pp.1216~1225 (2009), Wiley[DOI]
- L Stingl, "Novel HSP90 inhibitors, NVP-AUY922 and NVP-BEP800, radiosensitise tumour cells through cell-cycle impairment, increased DNA damage and repair protraction", British Journal of Cancer, 102(11), pp.1578~1591 (2010), Springer Nature[DOI]
- Wenjie Luo, "Heat shock protein 90 in neurodegenerative diseases", Molecular Neurodegeneration, 5(1), pp.24~ (2010), Springer Nature[DOI]
- M.T. Dillon, "Selective Targeting of the G2", M Cell Cycle Checkpoint to Improve the Therapeutic Index of Radiotherapy, 2014, pp.26(5), 257~265[DOI]
- Cheng-Zhong Zhang, "Chromothripsis from DNA damage in micronuclei", Nature, 522(7555), pp.179~184 (2015), Springer Nature[DOI]
- DA-HU WANG, "Geldanamycin mediates the apoptosis of gastric carcinoma cells through inhibition of EphA2 protein expression", Oncology Reports, 32(6), pp.2429~2436 (2014), Spandidos Publications[DOI]
- S. Shintani, "P53-dependent radiosensitizing effects of Hsp90 inhibitor 17-Allylamino-17-demethoxygeldanamycin on human oral squamous cell carcinoma cell lines", International Journal of Oncology, 29, pp.1111~1117 (2006), Spandidos Publications[DOI]