Hispidulin Enhances the Anti-Tumor Effects of Temozolomide in Glioblastoma by Activating AMPK

详细信息    查看全文

• 作者：YanGang Wang (1) r> WeiPing Liu (1) r> XiaoSheng He (1) r> Zhou Fei (1) r>r>1. Department of Neurosurgery ; Xijing Hospital of the Fourth Military Medical University ; No. 127 West Changle Road ; Xi鈥檃n ; 710032 ; Shaanxi ; People鈥檚 Republic of China r>
• 关键词：GBM ; TMZ ; Hispidulin ; AMPK
• 刊名：Cell Biochemistry and Biophysics
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：71
• 期：2
• 页码：701-706
• 全文大小：585 KB
• 参考文献：1. Ostrom, Q. T., et al. (2013). CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006鈥?010. / Neuro Oncology, / 15(Suppl 2), ii1鈥搃i56. rnal" href="http://dx.doi.org/10.1093/neuonc/not151" target="_blank" title="It opens in new window">CrossRef r> 2. Lin, G. S., et al. (2014). STAT3 serine 727 phosphorylation influences clinical outcome in glioblastoma. / International Journal of Clinical and Experimental Pathology, / 7(6), 3141鈥?149. r> 3. Stupp, R., et al. (2005). Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. / New England Journal of Medicine, / 352(10), 987鈥?96. rnal" href="http://dx.doi.org/10.1056/NEJMoa043330" target="_blank" title="It opens in new window">CrossRef r> 4. Quick, A., et al. (2010). Current therapeutic paradigms in glioblastoma. / Reviews on Recent Clinical Trials, / 5(1), 14鈥?7. rnal" href="http://dx.doi.org/10.2174/157488710790820544" target="_blank" title="It opens in new window">CrossRef r> 5. Chamberlain, M. C. (2010). Temozolomide: Therapeutic limitations in the treatment of adult high-grade gliomas. / Expert Review of Neurotherapeutics, / 10(10), 1537鈥?544. rnal" href="http://dx.doi.org/10.1586/ern.10.32" target="_blank" title="It opens in new window">CrossRef r> 6. Zhang, J., Stevens, M. F., & Bradshaw, T. D. (2012). Temozolomide: Mechanisms of action, repair and resistance. / Current Molecular Pharmacology, / 5(1), 102鈥?14. rnal" href="http://dx.doi.org/10.2174/1874467211205010102" target="_blank" title="It opens in new window">CrossRef r> 7. Tentori, L., & Graziani, G. (2009). Recent approaches to improve the antitumor efficacy of temozolomide. / Current Medicinal Chemistry, / 16(2), 245鈥?57. rnal" href="http://dx.doi.org/10.2174/092986709787002718" target="_blank" title="It opens in new window">CrossRef r> 8. Bourdillat, B., et al. (1988). Mechanism of action of hispidulin, a natural flavone, on human platelets. / Progress in Clinical and Biological Research, / 280, 211鈥?14. r> 9. He, L., et al. (2011). Hispidulin, a small flavonoid molecule, suppresses the angiogenesis and growth of human pancreatic cancer by targeting vascular endothelial growth factor receptor 2-mediated PI3聽K/Akt/mTOR signaling pathway. / Cancer Science, / 102(1), 219鈥?25. rnal" href="http://dx.doi.org/10.1111/j.1349-7006.2010.01778.x" target="_blank" title="It opens in new window">CrossRef r> 10. Tan, R. X., et al. (1999). Mono- and sesquiterpenes and antifungal constituents from Artemisia species. / Planta Medica, / 65(1), 64鈥?7. rnal" href="http://dx.doi.org/10.1055/s-1999-13965" target="_blank" title="It opens in new window">CrossRef r> 11. Yu, C. Y., et al. (2013). Potential Therapeutic Role of Hispidulin in Gastric Cancer through Induction of Apoptosis via NAG-1 Signaling. / Evidence-Based Complementary and Alternative Medicine, / 2013, 518301. r> 12. Gao, H., Wang, H., & Peng, J. (2014). Hispidulin induces apoptosis through mitochondrial dysfunction and inhibition of P13聽k/Akt signalling pathway in HepG2 cancer cells. / Cell Biochemistry and Biophysics, / 69(1), 27鈥?4. rnal" href="http://dx.doi.org/10.1007/s12013-013-9762-x" target="_blank" title="It opens in new window">CrossRef r> 13. Yang, J. M., et al. (2010). Hispidulin sensitizes human ovarian cancer cells to TRAIL-induced apoptosis by AMPK activation leading to Mcl-1 block in translation. / Journal of Agriculture and Food Chemistry, / 58(18), 10020鈥?0026. rnal" href="http://dx.doi.org/10.1021/jf102304g" target="_blank" title="It opens in new window">CrossRef r> 14. Lin, Y. C., et al. (2010). Hispidulin potently inhibits human glioblastoma multiforme cells through activation of AMP-activated protein kinase (AMPK). / Journal of Agriculture and Food Chemistry, / 58(17), 9511鈥?517. rnal" href="http://dx.doi.org/10.1021/jf1019533" target="_blank" title="It opens in new window">CrossRef r> 15. Cheng, H., et al. (2011). In vitro sequence-dependent synergism between paclitaxel and gefitinib in human lung cancer cell lines. / Cancer Chemotherapy and Pharmacology, / 67(3), 637鈥?46. rnal" href="http://dx.doi.org/10.1007/s00280-010-1347-4" target="_blank" title="It opens in new window">CrossRef r> 16. Huang, H., et al. (2011). Gambogic acid enhances proteasome inhibitor-induced anticancer activity. / Cancer Letters, / 301(2), 221鈥?28. rnal" href="http://dx.doi.org/10.1016/j.canlet.2010.12.015" target="_blank" title="It opens in new window">CrossRef r> 17. Chou, T. C., & Talalay, P. (1984). Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. / Advances in Enzyme Regulation, / 22, 27鈥?5. rnal" href="http://dx.doi.org/10.1016/0065-2571(84)90007-4" target="_blank" title="It opens in new window">CrossRef r> 18. Kopelovich, L., et al. (2007). The mammalian target of rapamycin pathway as a potential target for cancer chemoprevention. / Cancer Epidemiology Biomarkers & Prevention, / 16(7), 1330鈥?340. rnal" href="http://dx.doi.org/10.1158/1055-9965.EPI-07-0045" target="_blank" title="It opens in new window">CrossRef r> 19. Garami, A., et al. (2003). Insulin activation of Rheb, a mediator of mTOR/S6聽K/4E-BP signaling, is inhibited by TSC1 and 2. / Molecular Cell, / 11(6), 1457鈥?466. rnal" href="http://dx.doi.org/10.1016/S1097-2765(03)00220-X" target="_blank" title="It opens in new window">CrossRef r> 20. Zhang, J. F., et al. (2007). Rapamycin inhibits cell growth by induction of apoptosis on hepatocellular carcinoma cells in vitro. / Transplant Immunology, / 17(3), 162鈥?68. rnal" href="http://dx.doi.org/10.1016/j.trim.2006.12.003" target="_blank" title="It opens in new window">CrossRef r> 21. Romano, M. F., et al. (2004). Rapamycin inhibits doxorubicin-induced NF-kappaB/Rel nuclear activity and enhances the apoptosis of melanoma cells. / European Journal of Cancer, / 40(18), 2829鈥?836. rnal" href="http://dx.doi.org/10.1016/j.ejca.2004.08.017" target="_blank" title="It opens in new window">CrossRef r> 22. Yuan, Y., et al. (2012). Resveratrol enhances the antitumor effects of temozolomide in glioblastoma via ROS-dependent AMPK-TSC-mTOR signaling pathway. / CNS Neuroscience & Therapeutics, / 18(7), 536鈥?46. rnal" href="http://dx.doi.org/10.1111/j.1755-5949.2012.00319.x" target="_blank" title="It opens in new window">CrossRef r> 23. Gong, A., et al. (2014). Aplysin enhances temozolomide sensitivity in glioma cells by increasing miR-181 level. / Cancer Chemotherapy and Pharmacology, / 74(3), 531鈥?38. rnal" href="http://dx.doi.org/10.1007/s00280-014-2534-5" target="_blank" title="It opens in new window">CrossRef r> 24. Kunnumakkara, A. B., et al. (2008). Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor-kappaB-regulated gene products. / Clinical Cancer Research, / 14(7), 2128鈥?136. rnal" href="http://dx.doi.org/10.1158/1078-0432.CCR-07-4722" target="_blank" title="It opens in new window">CrossRef r> 25. Saha, A. K., et al. (2006). AMPK regulation of the growth of cultured human keratinocytes. / Biochemical and Biophysical Research Communications, / 349(2), 519鈥?24. rnal" href="http://dx.doi.org/10.1016/j.bbrc.2006.08.107" target="_blank" title="It opens in new window">CrossRef r> 26. Motoshima, H., et al. (2006). AMPK and cell proliferation鈥揂MPK as a therapeutic target for atherosclerosis and cancer. / Journal of Physiology, / 574(Pt 1), 63鈥?1. rnal" href="http://dx.doi.org/10.1113/jphysiol.2006.108324" target="_blank" title="It opens in new window">CrossRef r> 27. Yu, S. Y., et al. (2009). Inhibition of cervical cancer cell growth through activation of upstream kinases of AMP-activated protein kinase. / Tumour Biology, / 30(2), 80鈥?5. rnal" href="http://dx.doi.org/10.1159/000216843" target="_blank" title="It opens in new window">CrossRef r> 28. Inoki, K., Zhu, T., & Guan, K. L. (2003). TSC2 mediates cellular energy response to control cell growth and survival. / Cell, / 115(5), 577鈥?90. rnal" href="http://dx.doi.org/10.1016/S0092-8674(03)00929-2" target="_blank" title="It opens in new window">CrossRef r> 29. Wang, W., & Guan, K. L. (2009). AMP-activated protein kinase and cancer. / Acta Physiologica (Oxf), / 196(1), 55鈥?3. rnal" href="http://dx.doi.org/10.1111/j.1748-1716.2009.01980.x" target="_blank" title="It opens in new window">CrossRef r> 30. Cheng, S. W., et al. (2004). Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status. / Journal of Biological Chemistry, / 279(16), 15719鈥?5722. rnal" href="http://dx.doi.org/10.1074/jbc.C300534200" target="_blank" title="It opens in new window">CrossRef r>
• 刊物主题：Biochemistry, general; Pharmacology/Toxicology; Biotechnology; Cell Biology; Biophysics and Biological Physics;
• 出版者：Springer US
• ISSN：1559-0283

文摘

Glioblastoma is an aggressive malignancy, which is notorious for its poor prognosis. Although Temozolomide (TMZ) has been showed to be an effective chemotherapeutic agent for glioblastoma treatment, the response rate is far from satisfactory. As a natural compound with anti-cancer activity against a variety of cancers, Hispidulin is a good candidate drug for combination therapy. This study is designed to determine whether Hispidulin could potentiate the anti-tumor activity of TMZ in glioblastoma. Cell proliferation and apoptosis were determined by MTT assay and Hoechst staining, respectively. Expression of proteins relevant to apoptosis and proliferation was detected by Western blotting. Our in vitro assays showed that Hispidulin enhanced the anti-tumor activity of TMZ in glioblastoma by both inhibiting cell proliferation and inducing cell apoptosis. The anti-tumor activity of Hispidulin and the enhanced TMZ anti-tumor activity by Hispidulin induced the activation of AMPK signaling pathway. Our results showed that Hispidulin, by activating AMPK, exhibited anti-tumor activity and potentiated the anti-tumor activity of TMZ in glioblastoma. Although further preclinical and clinical studies are needed, this study provides insight for using Hispidulin as a chemosensitizing agent in clinic settings.