17-Demethoxy-reblastatin, an Hsp90 inhibitor, induces mitochondria-mediated apoptosis through downregulation of Mcl-1 in human hepatocellular carcinoma cells

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• 作者：Surong Zhao ; Hongmei Li ; Chenchen Jiang…
• 关键词：Hepatocellular carcinoma ; 17 ; Demethoxy ; reblastatin ; Apoptosis ; Myeloid cell leukemia ; 1
• 刊名：Journal of Bioenergetics and Biomembranes
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：47
• 期：5
• 页码：373-381
• 全文大小：4,177 KB
• 参考文献：Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281:1322–1326CrossRef
  Cervello M, Mccubrey JA, Cusimano A, Lampiasi N, Azzolina A, Montalto G (2012) Targeted therapy for hepatocellular carcinoma: novel agents on the horizon. Oncotarget 3:236–260CrossRef
  Chen D, Shen A, Li J, Shi F, Chen W, Ren J et al (2014) Discovery of potent N-(isoxazol-5-yl)amides as HSP90 inhibitors. Eur J Med Chem 87:765–781CrossRef
  Da Silva VC, Ramos CH (2012) The network interaction of the human cytosolic 90 kDa heat shock protein Hsp90: a target for cancer therapeutics. J Proteomics 75:2790–2802CrossRef
  Dean E, Greystoke A, Ranson M, Dive C (2012) Biomarkers of cell death applicable to early clinical trials. Exp Cell Res 318:1252–1259CrossRef
  Flores A, Marrero JA (2014) Emerging trends in hepatocellular carcinoma: focus on diagnosis and therapeutics. Clin Med Insights Oncol 8:71–76
  Gauthier A, Ho M (2013) Role of sorafenib in the treatment of advanced hepatocellular carcinoma: an update. Hepatol Res 43:147–154CrossRef
  Green DR (2005) Apoptotic pathways: ten minutes to dead. Cell 121:671–674CrossRef
  Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70CrossRef
  Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC, Burrows FJ (2003) A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 425:407–410CrossRef
  Kamal A, Boehm MF, Burrows FJ (2004) Therapeutic and diagnostic implications of Hsp90 activation. Trends Mol Med 10:283–290CrossRef
  Kim T, Keum G, Pae AN (2013) Discovery and development of heat shock protein 90 inhibitors as anticancer agents: a review of patented potent geldanamycin derivatives. Expert Opin Ther Pat 23:919–943CrossRef
  Leanza L, Henry B, Sassi N, Zoratti M, Chandy KG, Gulbins E, Szabo I (2012) Inhibitors of mitochondrial Kv1.3 channels induce Bax/Bak-independent death of cancer cells. EMBO Mol Med 4:577–593CrossRef
  Liu Q, Wang HG (2012) Anti-cancer drug discovery and development: Bcl-2 family small molecule inhibitors. Commun Integr Biol 5:557–565CrossRef
  Martinou JC, Green DR (2001) Breaking the mitochondrial barrier. Nat Rev Mol Cell Biol 2:63–67CrossRef
  Mohana-Kumaran N, Hill DS, Allen JD, Haass NK (2014) Targeting the intrinsic apoptosis pathway as a strategy for melanoma therapy. Pigment Cell Melanoma Res 27:525–539CrossRef
  Neckers L, Mimnaugh E, Schulte TW (1999) Hsp90 as an anti-cancer target. Drug Resist Updat 2:165–172CrossRef
  Pearce AF, Lyles DS (2009) Vesicular stomatitis virus induces apoptosis primarily through Bak rather than Bax by inactivating Mcl-1 and Bcl-XL. J Virol 83:9102–9112CrossRef
  Quinn BA, Dash R, Azab B, Sarkar S, Das SK, Kumar S et al (2011) Targeting Mcl-1 for the therapy of cancer. Expert Opin Investig Drugs 20:1397–1411CrossRef
  Shimazu T, Degenhardt K, Nur EKA, Zhang J, Yoshida T, Zhang Y et al (2007) NBK/BIK antagonizes MCL-1 and BCL-XL and activates BAK-mediated apoptosis in response to protein synthesis inhibition. Genes Dev 21:929–941CrossRef
  Shin JC, Na Z, Lee DH, Kim WC, Lee K, Shen YM et al (2008) Characterization of tailoring genes involved in the modification of geldanamycin polyketide in Streptomyces hygroscopicus JCM4427. J Microbiol Biotechnol 18:1101–1108
  Supko JG, Hickman RL, Grever MR, Malspeis L (1995) Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother Pharmacol 36:305–315CrossRef
  Taipale M, Jarosz DF, Lindquist S (2010) HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat Rev Mol Cell Biol 11:515–528CrossRef
  Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM (1994) Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A 91:8324–8328CrossRef
  Wu CZ, Jang JH, Ahn JS, Hong YS (2012) New geldanamycin analogs from Streptomyces hygroscopicus. J Microbiol Biotechnol 22:1478–1481CrossRef
  Zhang H, Burrows F (2004) Targeting multiple signal transduction pathways through inhibition of Hsp90. J Mol Med (Berl) 82:488–499
  Zhang W, Liu S, Liu K, Ji B, Wang Y, Liu Y (2014) Knockout of ADAM10 enhances sorafenib antitumor activity of hepatocellular carcinoma in vitro and in vivo. Oncol Rep 32:1913–1922
  Zhao Q, Wu CZ, Lee JK, Zhao SR, Li HM, Huo Q et al (2014) Anticancer effects of the Hsp90 inhibitor 17-demethoxy-reblastatin in human breast cancer MDA-MB-231 cells. J Microbiol Biotechnol 24:914–920
  Zheng Y, Gery S, Sun H, Shacham S, Kauffman M, Koeffler HP (2014) KPT-330 inhibitor of XPO1-mediated nuclear export has anti-proliferative activity in hepatocellular carcinoma. Cancer Chemother Pharmacol 74:487–495CrossRef
  Zhuo L, Liu J, Wang B, Gao M, Huang A (2013) Differential miRNA expression profiles in hepatocellular carcinoma cells and drug-resistant sublines. Oncol Rep 29:555–562
  
• 作者单位：Surong Zhao (1)
  Hongmei Li (1)
  Chenchen Jiang (2)
  Tao Ma (1)
  Chengzhu Wu (1)
  Qiang Huo (1)
  Hao Liu (1)
  
  1. Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China
  2. Priority Research Center for Cancer Research, University of Newcastle, Newcastle, Australia
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Bioorganic Chemistry
  Biochemistry
  Animal Anatomy, Morphology and Histology
  Animal Biochemistry
  Organic Chemistry
  
• 出版者：Springer New York
• ISSN：1573-6881

文摘

Heat shock protein 90 (Hsp90) is an attractive therapeutic target. Geldanamycin (GA), the first identified Hsp90 inhibitor, exhibited potent antitumor activity, but possessed significant hepatotoxicity. To overcome the hepatotoxicity derived from the quinone structure of GA, a non-quinone GA derivative 17-demethoxy-reblastatin (17-DR) was obtained from a genetically modified strain of Streptomyces hygroscopicus. In the present study, we examined the anticancer effects of 17-DR on human hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721, and its underlying mechanisms. The results indicated that 17-DR could concentration-dependently inhibit the proliferation, and decrease the colony formation in HCC cells. It also induced significant apoptosis in HCC cells, which was mediated by mitochondria via a caspase-dependent pathway. The mechanisms involved in 17-DR-induced apoptosis included the downregulation of myeloid cell leukemia-1 (Mcl-1), and upregulation of Bcl-2 antagonist killer 1 (Bak). And the upregulated Bak expression resulted from downregulation of Mcl-1 played an essential role in this process. Taken together, these results indicated that 17-DR possessed potent anticancer effects on HCC cells by inhibiting cell proliferation and inducing apoptosis.