Startseite Medizin Current insights and future perspectives of hypoxia-inducible factor-targeted therapy in cancer
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Current insights and future perspectives of hypoxia-inducible factor-targeted therapy in cancer

  • Thekkuttuparambil A. Ajith EMAIL logo
Veröffentlicht/Copyright: 27. September 2018
Journal of Basic and Clinical Physiology and Pharmacology
Aus der Zeitschrift Journal of Basic and Clinical Physiology and Pharmacology Band 30 Heft 1

Abstract

Hypoxia-inducible factors (HIFs) are transcription factors that are expressed in the hypoxic tumor microenvironment. They are involved in the cellular adaptations by improving the metabolism of glucose and enhance the expression of vascular endothelial growth factor, platelet-derived growth factor and angiopoietin, thereby they play a pivotal role in the angiogenesis. Hypoxia can increase the expression of nuclear factor-kappa B which promotes the pro-inflammatory status. Abnormally high angiogenesis, inflammation, antiapoptosis and anaerobic glycolysis can augment the progression and metastasis of tumor. Hence, HIFs remain one of the promising antiangiogenic agents as well as a direct target for interfering with the energetic of cancer cells in order to regulate the tumor growth. Previous studies found agents like topotecan, acriflavine and benzophenone-1B etc. to block the HIF-α mediated angiogenesis. The effect is mediated through interfering any one of the processes in the activation of HIF such as nuclear translocation of HIF-1α; dimerization of HIF-1α with β in the nucleus; HIF-1α/HIF-2α mediated induction of VEGF or translation of HIF-1α mRNA. Despite the experimental studies on the inhibitory molecules of HIFs, none of them are available for the clinical use. This review article discusses the recent update on the HIF-targeted therapy in cancer.

Keywords: angiogenesis; apoptosis; clear cell renal cell carcinoma; hypoxia; hypoxia-inducible factor; normoxia; nuclear factor-kappa B
Corresponding author: Dr. Thekkuttuparambil A. Ajith, PhD, Professor Biochemistry, Department of Biochemistry, Amala Institute of Medical Sciences, Amala Nagar, Thrissur-680 555, Kerala, India, Fax: +91-487-2307969

  1. Author contributions: The author has accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Padhani AR, Krohn KA, Lewis JS, Alber M. Imaging oxygenation of human tumours. Eur Radiol 2007;17:861–72.10.1007/s00330-006-0431-ySuche in Google Scholar PubMed

2. Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE. Hypoxia-inducible nuclear factors bind to an enhancer element located 3′ to the human erythropoietin gene. Proc Natl Acad Sci USA 1991;88:5680–4.10.1073/pnas.88.13.5680Suche in Google Scholar

3. Semenza GL. Hydroxylation of HIF-1: oxygen sensing at the molecular level. Physiology (Bethesda) 2004;19:176–82.10.1152/physiol.00001.2004Suche in Google Scholar PubMed

4. Cramer T, Yamanishi Y, Clausen BE, Förster I, Pawlinski R, Mackman N, et al. HIF-1alpha is essential for myeloid cell-mediated inflammation. Cell 2003;112:645–57.10.1016/S0092-8674(03)00154-5Suche in Google Scholar PubMed

5. Suzuki N, Gradin K, Poellinger L, Yamamoto M. Regulation of hypoxia-inducible gene expression after HIF activation. Exp Cell Res 2017;356:182–6.10.1016/j.yexcr.2017.03.013Suche in Google Scholar PubMed

6. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999;399:271–5.10.1038/20459Suche in Google Scholar PubMed

7. Thirusangu P, Vigneshwaran V, Prashanth T, Vijay Avin BR, Malojirao VH, Rakesh H, et al. BP-1T, an antiangiogenic benzophenone-thiazole pharmacophore, counteracts HIF-1 signalling through p53/MDM2-mediated HIF-1α proteasomal degradation. Angiogenesis 2017;20:55–71.10.1007/s10456-016-9528-3Suche in Google Scholar PubMed

8. Chowdhury AR, Long A, Fuchs SY, Rustgi A, Avadhani NG. Mitochondrial stress-induced p53 attenuates HIF-1α activity by physical association and enhanced ubiquitination. Oncogene 2017;36:397–409.10.1038/onc.2016.211Suche in Google Scholar PubMed PubMed Central

9. Koh MY, Darnay BG, Powis G. Hypoxia-associated factor, a novel E3-ubiquitin ligase, binds and ubiquitinates hypoxia-inducible factor 1alpha, leading to its oxygen-independent degradation. Mol Cell Biol 2008;28:7081–95.10.1128/MCB.00773-08Suche in Google Scholar PubMed PubMed Central

10. Koh MY, Lemos R Jr, Liu X, Powis G. The hypoxia-associated factor switches cells from HIF-1α- to HIF-2α-dependent signaling promoting stem cell characteristics, aggressive tumor growth and invasion. Cancer Res 2011;71:4015–27.10.1158/0008-5472.CAN-10-4142Suche in Google Scholar PubMed PubMed Central

11. Schroedl C, McClintock DS, Budinger GR, Chandel NS. Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species. Am J Physiol Lung Cell Mol Physiol 2002;283:L922–31.10.1152/ajplung.00014.2002Suche in Google Scholar PubMed

12. Olson N, van der Vliet A. Interactions between nitric oxide and hypoxia-inducible factor signaling pathways in inflammatory disease. Nitric Oxide 2011;25:125–37.10.1016/j.niox.2010.12.010Suche in Google Scholar PubMed PubMed Central

13. Koong AC, Chen EY, Giaccia AJ. Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues. Cancer Res 1994;54:1425–30.Suche in Google Scholar PubMed

14. Shahneh FZ, Baradaran B, Zamani F, Aghebati-Maleki L. Tumor angiogenesis and anti-angiogenic therapies. Hum Antibodies 2013;22:15–9.10.3233/HAB-130267Suche in Google Scholar PubMed

15. Wang V, Davis DA, Haque M, Huang LE, Yarchoan R. Differential gene up-regulation by hypoxia-inducible factor-1alpha and hypoxia-inducible factor-2alpha in HEK293T cells. Cancer Res 2005;65:3299–306.10.1158/0008-5472.CAN-04-4130Suche in Google Scholar PubMed

16. Singh M, Devi U, Roy S, Gupta PS, Saraf SA, Kaithwas G. Prolyl hydroxylase mediated inhibition of fatty acid synthase to combat tumor growth in mammary gland carcinoma.Breast Cancer 2016;23:820–9.10.1007/s12282-016-0683-6Suche in Google Scholar PubMed

17. Downes NL, Laham-Karam N, Kaikkonen MU, Ylä-Herttuala S. Differential but complementary HIF1α and HIF2α transcriptional regulation. Mol Ther 2018;26:1735–45.10.1016/j.ymthe.2018.05.004Suche in Google Scholar PubMed PubMed Central

18. Murugesan T, Rajajeyabalachandran G, Kumar S, Nagaraju S, Jegatheesan SK. Targeting HIF-2α as therapy for advanced cancers. Drug Discov Today 2018;23:1444–51.10.1016/j.drudis.2018.05.003Suche in Google Scholar PubMed

19. Guan Z, Ding C, Du Y, Zhang K, Zhu JN, Zhang T, et al. HAF drives the switch of HIF-1α to HIF-2α by activating the NF-κB pathway, leading to malignant behavior of T24 bladder cancer cells. Int J Oncol 2014;44:393–402.10.3892/ijo.2013.2210Suche in Google Scholar PubMed PubMed Central

20. Yuan G, Nanduri J, Khan S, Semenza GL, Prabhakar NR. Induction of HIF-1alpha expression by intermittent hypoxia: involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR. J Cell Physiol 2008;217:674–85.10.1002/jcp.21537Suche in Google Scholar PubMed PubMed Central

21. Zhang L, Qu Y, Zhang X, Yang C, Mao M, Mu D. Relationship between hypoxia-inducible factor-1alpha expression and extracellular signal-regulated kinase in hypoxic-ischemic cortical neurons. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2009;23:954–8.Suche in Google Scholar PubMed

22. Sandau KB, Faus HG, Brüne B. Induction of hypoxia-inducible-factor 1 by nitric oxide is mediated via the PI 3K pathway. Cell Biochem Biophys Res Commun 2000;278:263–7.10.1006/bbrc.2000.3789Suche in Google Scholar PubMed

23. Deng W, Feng X, Li X, Wang D, Sun L. Hypoxia-inducible factor 1 in autoimmune diseases. Cell Immunol 2016;303:7–15.10.1016/j.cellimm.2016.04.001Suche in Google Scholar PubMed

24. Thomson AW, Turnquist HR, Raimondi G. Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol 2009;9:324–37.10.1038/nri2546Suche in Google Scholar PubMed PubMed Central

25. Jantsch J, Wiese M, Schödel J, Castiglione K, Gläsner J, Kolbe S, et al. Toll-like receptor activation and hypoxia use distinct signaling pathways to stabilize hypoxia-inducible factor 1α (HIF1A) and result in differential HIF1A-dependent gene expression. J Leukoc Biol 2011;90:551–62.10.1189/jlb.1210683Suche in Google Scholar PubMed

26. Thornton RD, Lane P, Borghaei RC, Pease EA, Caro J, Mochan E. Interleukin 1 induces hypoxia-inducible factor 1 in human gingival and synovial fibroblasts. Biochem J 2000;350:307–12.10.1042/bj3500307Suche in Google Scholar PubMed

27. Sang N, Stiehl DP, Bohensky J, Leshchinsky I, Srinivas V, Caro J. MAPK signaling up-regulates the activity of hypoxia-inducible factors by its effects on p300. J Biol Chem 2003;278:14013–9.10.1074/jbc.M209702200Suche in Google Scholar PubMed PubMed Central

28. Hellwig-Bürgel T, Rutkowski K, Metzen E, Fandrey J, Jelkmann W. Interleukin-1beta and tumor necrosis factor-alpha stimulate DNA binding of hypoxia-inducible factor-1. Blood 1999;94:1561–7.10.1182/blood.V94.5.1561Suche in Google Scholar PubMed

29. Kuo HP, Lee DF, Xia W, Wei Y, Hung MC. TNFalpha induces HIF-1alpha expression through activation of IKK beta. Biochem Biophys Res Commun 2009;389:640–4.10.1016/j.bbrc.2009.09.042Suche in Google Scholar PubMed PubMed Central

30. Hui AS, Bauer AL, Striet JB, Schnell PO, Czyzyk-Krzeska MF. Calcium signaling stimulates translation of HIF-alpha during hypoxia. FASEB J 2006;20:466–75.10.1096/fj.05-5086comSuche in Google Scholar PubMed

31. Yuan G, Nanduri J, Bhasker CR, Semenza GL, Prabhakar NR. Ca2+/calmodulin kinase-dependent activation of hypoxia inducible factor 1 transcriptional activity in cells subjected to intermittent hypoxia. J Biol Chem 2005;280:4321–8.10.1074/jbc.M407706200Suche in Google Scholar PubMed

32. Divolis G, Mavroeidi P, Mavrofrydi O, Papazafiri P. Differential effects of calcium on PI3K-Akt and HIF-1α survival pathways. Cell Biol Toxicol 2016;32:437–49.10.1007/s10565-016-9345-xSuche in Google Scholar PubMed

33. Indo HP, Hawkins CL, Nakanishi I, Matsumoto KI, Matsui H, Suenaga S, et al. Role of Mitochondrial Reactive Oxygen Species in the Activation of Cellular Signals, Molecules, and Function. Handb Exp Pharmacol 2017;240:439–56.10.1007/164_2016_117Suche in Google Scholar PubMed

34. Koido M, Haga N, Furuno A, Tsukahara S, Sakurai J, Tani Y, et al. Mitochondrial deficiency impairs hypoxic induction of HIF-1 transcriptional activity and retards tumor growth. Oncotarget 2017;8:11841–54.10.18632/oncotarget.14415Suche in Google Scholar PubMed PubMed Central

35. Han S, Xu W, Wang Z, Qi X, Wang Y, Ni Y, et al. Crosstalk between the HIF-1 and Toll-like receptor/nuclear factor-κB pathways in the oral squamous cell carcinoma microenvironment. Oncotarget 2016;7:37773–89.10.18632/oncotarget.9329Suche in Google Scholar PubMed PubMed Central

36. Gradin K, Takasaki C, Fujii-Kuriyama Y, Sogawa K. The transcriptional activation function of the HIF-like factor requires phosphorylation at a conserved threonine. J Biol Chem 2002;277:23508–14.10.1074/jbc.M201307200Suche in Google Scholar PubMed

37. Antonsson C, Whitelaw ML, McGuire J, Gustafsson JA, Poellinger L. Distinct roles of the molecular chaperone hsp90 in modulating dioxin receptor function via the basic helix-loop-helix and PAS domains. Mol Cell Biol 1995;15:756–65.10.1128/MCB.15.2.756Suche in Google Scholar PubMed PubMed Central

38. Yu L, Lu M, Jia D, Ma J, Ben-Jacob E, Levine H, et al. Modeling the Genetic Regulation of Cancer Metabolism: Interplay Between Glycolysis and Oxidative Phosphorylation. Cancer Res 2017;77:1564–74.10.1158/0008-5472.CAN-16-2074Suche in Google Scholar PubMed PubMed Central

39. Starska K, Forma E, Jóźwiak P, Bryś M, Lewy-Trenda I, Brzezińska-Błaszczyk E, et al. Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer – the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis. Tumour Biol 2015;36:2309–21.10.1007/s13277-014-2838-4Suche in Google Scholar PubMed PubMed Central

40. Schwab LP, Peacock DL, Majumdar D, Ingels JF, Jensen LC, Smith KD, et al. Hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer. Breast Cancer Res 2012;14:R6.10.1186/bcr3087Suche in Google Scholar PubMed PubMed Central

41. Helczynska K, Larsson AM, Holmquist Mengelbier L, Bridges E, Fredlund E, Borgquist S, et al. Hypoxia-inducible factor-2alpha correlates to distant recurrence and poor outcome in invasive breast cancer. Cancer Res 2008;68:9212–20.10.1158/0008-5472.CAN-08-1135Suche in Google Scholar PubMed

42. Gilkes DM, Semenza GL. Role of hypoxia-inducible factors in breast cancer metastasis. Future Oncol 2013;9:1623–36.10.2217/fon.13.92Suche in Google Scholar PubMed PubMed Central

43. Gilkes DM. Implications of Hypoxia in Breast Cancer Metastasis to Bone. Int J Mol Sci 2016;17:pii: E1669.10.3390/ijms17101669Suche in Google Scholar PubMed PubMed Central

44. Cui XY, Skretting G, Tinholt M, Stavik B, Dahm AE, Sahlberg KK, et al. A novel hypoxia response element regulates oxygen-related repression of tissue factor pathway inhibitor in the breast cancer cell line MCF-7. Thromb Res 2017;157:111–6.10.1016/j.thromres.2017.07.013Suche in Google Scholar PubMed

45. Yeom CJ, Zeng L, Goto Y, Morinibu A, Zhu Y, Shinomiya K, et al. LY6E: a conductor of malignant tumor growth through modulation of the PTEN/PI3K/Akt/HIF-1 axis. Oncotarget 2016;7: 65837–48.10.18632/oncotarget.11670Suche in Google Scholar PubMed PubMed Central

46. Lv Y, Song Y, Ni C, Wang S, Chen Z, Shi X, et al. Over expression of lymphocyte antigen 6 complex, locus E in gastric cancer promotes cancer cell growth and metastasis. Cell Physiol Biochem 2018;45:1219–29.10.1159/000487453Suche in Google Scholar PubMed

47. Jeong YJ, Jung JW, Cho YY, Park SH, Oh HK, Kang S. Correlation of hypoxia inducible transcription factor in breast cancer and SUVmax of F-18 FDG PET/CT. Nucl Med Rev Cent East Eur 2017;20:32–8.10.5603/NMR.a2016.0043Suche in Google Scholar PubMed

48. Alam MW, Persson CU, Reinbothe S, Kazi JU, Rönnstrand L, Wigerup C, et al. HIF2α contributes to antiestrogen resistance via positive bilateral crosstalk with EGFR in breast cancer cells. Oncotarget 2016;7:11238–50.10.18632/oncotarget.7167Suche in Google Scholar PubMed PubMed Central

49. Puppo M, Battaglia F, Ottaviano C, Delfino S, Ribatti D, Varesio L, et al. Topotecan inhibits vascular endothelial growth factor production and angiogenic activity induced by hypoxia in human neuroblastoma by targeting hypoxia-inducible factor-1alpha and -2alpha. Mol Cancer Ther 2008;7:1974–84.10.1158/1535-7163.MCT-07-2059Suche in Google Scholar PubMed

50. Sivridis E, Giatromanolaki A, Gatter KC, Harris AL, Koukourakis MI. Tumor and Angiogenesis Research Group. Association of hypoxia-inducible factors 1alpha and 2alpha with activated angiogenic pathways and prognosis in patients with endometrial carcinoma. Cancer 2002;95:1055–63.10.1002/cncr.10774Suche in Google Scholar PubMed

51. Giatromanolaki A, Sivridis E, Simopoulos C, Polychronidis A, Gatter KC, Harris AL, et al. Hypoxia inducible factors 1alpha and 2alpha are associated with VEGF expression and angiogenesis in gallbladder carcinomas. J Surg Oncol 2006;94:242–7.10.1002/jso.20443Suche in Google Scholar PubMed

52. Chen Y, Li C, Xie H, Fan Y, Yang Z, Ma J, et al. Infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating PI3K→AKT→GSK3β→AM signaling. Oncogene 2017;36: 2879–88.10.1038/onc.2016.442Suche in Google Scholar PubMed PubMed Central

53. Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003;9:669–76.10.1038/nm0603-669Suche in Google Scholar PubMed

54. Martínez-Sáez O, Gajate Borau P, Alonso-Gordoa T, Molina-Cerrillo J, Grande E. Targeting HIF-2 α in clear cell renal cell carcinoma: a promising therapeutic strategy. Crit Rev Oncol Hematol 2017;111:117–23.10.1016/j.critrevonc.2017.01.013Suche in Google Scholar PubMed

55. Shen C, Kaelin WG Jr. The VHL/HIF axis in clear cell renal carcinoma. Semin Cancer Biol 2013;23:18–25.10.1016/j.semcancer.2012.06.001Suche in Google Scholar PubMed PubMed Central

56. Cao MQ, Gao JR, Huang JF, You AB, Guo ZG, Zhou HY, et al. Effect of HIF-2α on regulating CDCP1 to promote hepatocellular carcinoma metastasis. Zhonghua Zhong Liu Za Zhi 2017;39: 18–23.Suche in Google Scholar PubMed

57. Knowles HJ. Hypoxia-induced fibroblast growth factor 11 stimulates osteoclast-mediated resorption of bone. Calcif Tissue Int 2017;100:382–91.10.1007/s00223-016-0228-1Suche in Google Scholar PubMed PubMed Central

58. Zhang B, Li YL, Zhao JL, Zhen O, Yu C, Yang BH, et al. Hypoxia-inducible factor-1 promotes cancer progression through activating AKT/Cyclin D1 signaling pathway in osteosarcoma. Biomed Pharmacother 2018;105:1–9.10.1016/j.biopha.2018.03.165Suche in Google Scholar PubMed

59. Yang X, Yin H, Zhang Y, Li X, Tong H, Zeng Y, et al. Hypoxia-induced autophagy promotes gemcitabine resistance in human bladder cancer cells through hypoxia-inducible factor 1α activation. Int J Oncol 2018;53:215–24.10.3892/ijo.2018.4376Suche in Google Scholar PubMed

60. Zhang N, Gong K, Yang XY, Xin DQ, Na YQ. Expression of hypoxia-inducible factor-1-alpha, hypoxia-inducible factor-2alpha and vascular endothelial growth factor in sporadic clear cell renal cell renal cell carcinoma and their significance in the pathogenesis thereof. Zhonghua Yi Xue Za Zhi 2006;86:1526–9.Suche in Google Scholar PubMed

61. Yin Q, Hung SC, Wang L, Lin W, Fielding JR, Rathmell WK, et al. Associations between tumor vascularity, vascular endothelial growth factor expression and PET/MRI radiomic signatures in primary clear-cell-renal-cell-carcinoma: proof-of-concept study. Sci Rep 2017;7:43356.10.1038/srep43356Suche in Google Scholar PubMed PubMed Central

62. Vachhani P, George S. VEGF inhibitors in renal cell carcinoma. Clin Adv Hematol Oncol 2016;14:1016–28.Suche in Google Scholar PubMed

63. Tannir NM, Schwab G, Grünwald V. Cabozantinib: an active novel multikinase inhibitor in renal cell carcinoma. Curr Oncol Rep 2017;19:14.10.1007/s11912-017-0566-9Suche in Google Scholar PubMed PubMed Central

64. Donskov F, Michaelson MD, Puzanov I, Davis MP, Bjarnason GA, Motzer RJ, et al. Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients. Br J Cancer 2015;113:1571–80.10.1038/bjc.2015.368Suche in Google Scholar PubMed PubMed Central

65. Cuvillier O. The therapeutic potential of HIF-2 antagonism in renal cell carcinoma. Transl Androl Urol 2017;6:131–3.10.21037/tau.2017.01.12Suche in Google Scholar PubMed PubMed Central

66. Lee K, Zhang H, Qian DZ, Rey S, Liu JO, Semenza GL. Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc Natl Acad Sci USA 2009;106:17910–5.10.1073/pnas.0909353106Suche in Google Scholar PubMed PubMed Central

67. Thirusangu P, Vigneshwaran V, Ranganatha VL, Vijay Avin BR, Khanum SA, Mahmood R, et al. A tumoural angiogenic gateway blocker, Benzophenone-1B represses the HIF-1α nuclear translocation and its target gene activation against neoplastic progression. Biochem Pharmacol 2017;125:26–40.10.1016/j.bcp.2016.11.009Suche in Google Scholar PubMed

68. Lee K, Qian DZ, Rey S, Wei H, Liu JO, Semenza GL. Anthracycline chemotherapy inhibits HIF-1 transcriptional activity and tumor-induced mobilization of circulating angiogenic cells. Proc Natl Acad Sci USA 2009;106:2353–8.10.1073/pnas.0812801106Suche in Google Scholar PubMed PubMed Central

69. Xiang GL, Zhu XH, Lin CZ, Wang LJ, Sun Y, Cao YW, et al. 125I seed irradiation induces apoptosis and inhibits angiogenesis by decreasing HIF-1α and VEGF expression in lung carcinoma xenografts. Oncol Rep 2017;37:3075–83.10.3892/or.2017.5521Suche in Google Scholar PubMed

70. Wang WM, Zhao ZL, Ma SR, Yu GT, Liu B, Zhang L, et al. Epidermal growth factor receptor inhibition reduces angiogenesis via hypoxia-inducible factor-1α and Notch1 in head neck squamous cell carcinoma. PLoS One 2015;10:e0119723.10.1371/journal.pone.0119723Suche in Google Scholar PubMed PubMed Central

71. Hussain I, Waheed S, Ahmad KA, Pirog JE, Syed V. Scutellaria baicalensis targets the hypoxia-inducible factor-1α and enhances cisplatin efficacy in ovarian cancer. J Cell Biochem 2018; doi: 10.1002/jcb.27063. [Epub ahead of print].10.1002/jcb.27063Suche in Google Scholar PubMed

72. Kuo YT, Jheng JH, Lo MC, Chen WL, Wang SG, Lee HM. Ferrous glycinate regulates cell energy metabolism by restricting hypoxia-induced factor-1α expression in human A549 cells. Free Radic Res 2018; doi: 10.1080/10715762.2018.1476691. [Epub ahead of print].10.1080/10715762.2018.1476691Suche in Google Scholar PubMed

73. Tang C, Lei H, Zhang J, Liu M, Jin J, Luo H, et al. Montelukast inhibits hypoxia inducible factor-1α translation in prostate cancer cells. Cancer Biol Ther 2018;19:715–21.10.1080/15384047.2018.1451279Suche in Google Scholar PubMed PubMed Central

74. Kobayashi Y, Oguro A, Imaoka S. Bisphenol A and its derivatives induce degradation of HIF-1alpha via the lysosomal pathway in human hepatocarcinoma cell line, Hep3B. Biol Pharm Bull 2018;41:374–82.10.1248/bpb.b17-00693Suche in Google Scholar PubMed

75. Greenberger LM, Horak ID, Filpula D, Sapra P, Westergaard M, Frydenlund HF, et al. A RNA antagonist of hypoxia-inducible factor-1alpha, EZN-2968, inhibits tumor cell growth. Mol Cancer Ther 2008;7:3598–608.10.1158/1535-7163.MCT-08-0510Suche in Google Scholar PubMed

76. Zhang H, Qian DZ, Tan YS, Lee K, Gao P, Ren YR, et al. Digoxin and other cardiac glycosides inhibit HIF-1alpha synthesis and block tumor growth. Proc Natl Acad Sci USA 2008;105:19579–86.10.1073/pnas.0809763105Suche in Google Scholar PubMed PubMed Central

77. Ashok BS, Ajith TA, Sivanesan S. Hypoxia-inducible factors as neuroprotective agent in Alzheimer’s disease. Clin Exp Pharmacol Physiol 2017;44:327–34.10.1111/1440-1681.12717Suche in Google Scholar PubMed

Received: 2017-10-01
Accepted: 2018-07-31
Published Online: 2018-09-27
Published in Print: 2018-12-19

©2019 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Immune response and inflammatory pathway of ulcerative colitis
  4. Current insights and future perspectives of hypoxia-inducible factor-targeted therapy in cancer
  5. Behavior and Neuroprotection
  6. Effect of caffeine on alcohol consumption and alcohol-induced conditioned place preference in rodents
  7. Reproduction
  8. Pubertal anabolic androgenic steroid exposure in male rats affects levels of gonadal steroids, mating frequency, and pregnancy outcome
  9. Dynamics of inflammatory reaction and oxidative stress across maternal serum, placenta and amniotic fluid in laboratory rats and the role played by genistein aglycone
  10. Cardiovascular-Pulmonary Interactions
  11. Local inhibition of carbonic anhydrase does not decrease sweat rate
  12. The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats
  13. Correlation between the blood level of irisin and the severity of acute myocardial infarction in exercise-trained rats
  14. Oxidative Stress
  15. Zataria multiflora extract and carvacrol affect cardiotoxicity induced by Adriamycin in rat
  16. Attenuation of oxidative stress and hepatic damage by white butterfly (Clerodendrum volubile) leaves in streptozotocin-induced diabetes in rats
  17. Proline supplementation mitigates the early stage of liver injury in bile duct ligated rats
  18. Pravastatin attenuates testicular damage induced by doxorubicin – a stereological and histopatological study
  19. Metabolism
  20. Re-establishing normal diet following high fat-diet-induced obesity reverses the altered salivary composition in Wistar rats
  21. Phytotherapy
  22. In vivo analgesic effect of different extracts of Hopea odorata leaves in mice and in silico molecular docking and ADME/T property analysis of some isolated compounds from this plant
  23. Hepatoprotective activity of Tamarindus indica Linn stem bark ethanolic extract against hepatic damage induced by co-administration of antitubercular drugs isoniazid and rifampicin in Sprague Dawley rats
  24. Case Report
  25. Drug-induced optic neuropathy in a case of extensively drug-resistant pulmonary tuberculosis
https://doi.org/10.1515/jbcpp-2017-0167
Schlagwörter für diesen Artikel
angiogenesis; apoptosis; clear cell renal cell carcinoma; hypoxia; hypoxia-inducible factor; normoxia; nuclear factor-kappa B

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Immune response and inflammatory pathway of ulcerative colitis
  4. Current insights and future perspectives of hypoxia-inducible factor-targeted therapy in cancer
  5. Behavior and Neuroprotection
  6. Effect of caffeine on alcohol consumption and alcohol-induced conditioned place preference in rodents
  7. Reproduction
  8. Pubertal anabolic androgenic steroid exposure in male rats affects levels of gonadal steroids, mating frequency, and pregnancy outcome
  9. Dynamics of inflammatory reaction and oxidative stress across maternal serum, placenta and amniotic fluid in laboratory rats and the role played by genistein aglycone
  10. Cardiovascular-Pulmonary Interactions
  11. Local inhibition of carbonic anhydrase does not decrease sweat rate
  12. The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats
  13. Correlation between the blood level of irisin and the severity of acute myocardial infarction in exercise-trained rats
  14. Oxidative Stress
  15. Zataria multiflora extract and carvacrol affect cardiotoxicity induced by Adriamycin in rat
  16. Attenuation of oxidative stress and hepatic damage by white butterfly (Clerodendrum volubile) leaves in streptozotocin-induced diabetes in rats
  17. Proline supplementation mitigates the early stage of liver injury in bile duct ligated rats
  18. Pravastatin attenuates testicular damage induced by doxorubicin – a stereological and histopatological study
  19. Metabolism
  20. Re-establishing normal diet following high fat-diet-induced obesity reverses the altered salivary composition in Wistar rats
  21. Phytotherapy
  22. In vivo analgesic effect of different extracts of Hopea odorata leaves in mice and in silico molecular docking and ADME/T property analysis of some isolated compounds from this plant
  23. Hepatoprotective activity of Tamarindus indica Linn stem bark ethanolic extract against hepatic damage induced by co-administration of antitubercular drugs isoniazid and rifampicin in Sprague Dawley rats
  24. Case Report
  25. Drug-induced optic neuropathy in a case of extensively drug-resistant pulmonary tuberculosis
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 9.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/jbcpp-2017-0167/html
Button zum nach oben scrollen