Statins as a Combatant for Treatment of Glioblastoma

  • ARATI GANESH JAYBHAYE Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India
  • Supriya Sangram Nikam Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India https://orcid.org/0009-0002-4506-2515
  • KALYANI PRANAV KAYANDE Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India
  • PRATIK Marotirao PATIL Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India
  • ANUSHKA Vijay SUROSHE Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India https://orcid.org/0009-0006-7505-7281
  • PAVAN Babasaheb ZALTE Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India https://orcid.org/0009-0004-0390-7721
  • SHRIPARNI Ashok BHUJBAL Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India https://orcid.org/0009-0005-1221-1846

Abstract

The competitive HMG-CoA reductase (HMGCR) inhibitors, commonly referred to as "statins," have been shown in preclinical tests to have promise anticancer characteristics in addition to being potent medications that lower cholesterol and lower cardiovascular risk. When combined with other cancer treatment strategies, statins seem to improve the treatment outcome for a variety of malignancies. After surgical resection followed by concomitant radiation and chemotherapy, the median overall survival (OS) for glioblastoma multiforme (GBM), a particularly lethal cerebral tumour, is only about one year. Due to their capacity to inhibit cell growth, survival, migration, metastasis, inflammation, and angiogenesis in both in vitro and in vivo investigations, statins have recently come to light as prospective adjuvant medications for the treatment of GBM. Statins' therapeutic effects on the survival of GBM patients are still debatable, though. When just focusing on the treatment of cancer, specifically GBM, this study intends to analyse and address some of the known effects of statin medicines, including concurrent statin therapy with chemotherapeutic agents.


Keywords: statin, glioblastoma, brain tumor, antitumor, cholesterol, apoptosis.

Keywords: statin, glioblastoma, brain tumor, antitumor, cholesterol, apoptosis

Downloads

Download data is not yet available.

Author Biographies

ARATI GANESH JAYBHAYE, Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

Supriya Sangram Nikam, Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

KALYANI PRANAV KAYANDE, Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

PRATIK Marotirao PATIL, Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

ANUSHKA Vijay SUROSHE, Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

PAVAN Babasaheb ZALTE, Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

SHRIPARNI Ashok BHUJBAL, Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

Department of Pharmaceutics, Sinhgad Institute of Pharmacy Narhe, Pune, India

References

1. Sahab-Negah S, Ariakia F, Jalili-Nik M, Afshari AR, Salehi S, Samini F, Rajabzadeh G, Gorji A. Curcumin loaded in niosomal nanoparticles improved the anti-tumor effects of free curcumin on glioblastoma stem-like cells: an in vitro study. Molecular Neurobiology. 2020 Aug;57:3391-411. https://doi.org/10.1007/s12035-020-01922-5
2. Afshari AR, Mollazadeh H, Henney NC, Jamialahmad T, Sahebkar A. Effects of statins on brain tumors: a review. In Seminars in Cancer Biology 2021 Aug 1 (Vol. 73, pp. 116- 133). Academic Press. https://doi.org/10.1016/j.semcancer.2020.08.002
3. Sodero AO, Barrantes FJ. Pleiotropic effects of statins on brain cells. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2020 Sep 1;1862(9):183340. https://doi.org/10.1016/j.bbamem.2020.183340
4. Miraglia E, Högberg J, Stenius U. Statins exhibit anticancer effects through modifications of the pAkt signaling pathway. International journal of oncology. 2012 Mar 1;40(3):867- 75. https://doi.org/10.3892/ijo.2011.1223
5. Laufs U, Kilter H, Konkol C, Wassmann S, Böhm M, Nickenig G. Impact of HMG CoA reductase inhibition on small GTPases in the heart. Cardiovascular research. 2002 Mar 1;53(4):911-20. https://doi.org/10.1016/S0008-6363(01)00540-5
6. Mo H, Jeter R, Bachmann A, Yount ST, Shen CL, Yeganehjoo H. The potential of isoprenoids in adjuvant cancer therapy to reduce adverse effects of statins. Frontiers in pharmacology. 2019 Jan 4;9:1515. https://doi.org/10.3389/fphar.2018.01515
7. Matzno S, Yasuda S, Juman S, Yamamoto Y, Nagareya-Ishida N, Nakabayashi T, Matsuyama K, Tazuya-Murayama K. Statin-induced apoptosis linked with membrane farnesylated Ras small G protein depletion, rather than geranylated Rho protein. Journal of pharmacy and pharmacology. 2005 Nov;57(11):1475-84. https://doi.org/10.1211/jpp.57.11.0014
8. Lu SE, Lin Y, Graber JM, Rotter D, Zhang L, Petersen GM, Demissie K, Lu-Yao G, Tan XL. Differential and joint effects of metformin and statins on overall survival of elderly patients with pancreatic adenocarcinoma: a large population-based study. Cancer Epidemiology, Biomarkers & Prevention. 2017 Aug 1;26(8):1225-32. https://doi.org/10.1158/1055-9965.EPI-17-0227
9. von Schuckmann LA, Khosrotehrani K, Ghiasvand R, Hughes MC, van der Pols JC, Malt M, Smithers BM, Green AC. Statins may reduce disease recurrence in patients with ulcerated primary melanoma. British Journal of Dermatology. 2020 Dec 1;183(6):1049- 55. https://doi.org/10.1111/bjd.19012
10. Xia DK, Hu ZG, Tian YF, Zeng FJ. Statin use and prognosis of lung cancer: a systematic review and meta-analysis of observational studies and randomized controlled trials. Drug design, development and therapy. 2019 Jan 23:405-22. https://doi.org/10.2147/DDDT.S187690
11. Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. New England Journal of Medicine. 2012 Nov 8;367(19):1792-802. https://doi.org/10.3390/cancers16071313
12. Tapia-Pérez JH, Sanchez-Aguilar M, Schneider T. The role of statins in neurosurgery. Neurosurgical Review. 2010 Jul; 33:259-70. https://doi.org/10.1007/s10143-010-0259-4
13. Tan P, Zhang C, Wei SY, Tang Z, Gao L, Yang L, Wei Q. Effect of statins type on incident prostate cancer risk: a meta-analysis and systematic review. Asian journal of andrology. 2017 Nov;19(6):666. DOI: 10.4103/1008-682X.190327
14. Gaber O, Eldessouki I, Hassan R, Magdy M, Morris JC, Karim NA. Retrospective Study of the Effect of Statins on the Outcome of Lung Cancer Patients, University of Cincinnati Experience. Asian Pacific journal of cancer prevention: APJCP. 2019;20(8):2391. DOI: 10.31557/APJCP.2019.20.8.2391
15. Afshari AR, Mollazadeh H, Henney NC, Jamialahmad T, Sahebkar A. Effects of statins on brain tumors: a review. In Seminars in Cancer Biology 2021 Aug 1 (Vol. 73, pp. 116- 133). Academic Press. https://doi.org/10.1016/j.semcancer.2020.08.002
16. Liu B, Yi Z, Guan X, Zeng YX, Ma F. The relationship between statins and breast cancer prognosis varies by statin type and exposure time: a meta-analysis. Breast cancer research and treatment. 2017 Jul; 164:1-1. https://doi.org/10.1007/s10549-017-4246-0
17. Röhrig F, Schulze A. The multifaceted roles of fatty acid synthesis in cancer. Nature Reviews Cancer. 2016 Nov;16(11):732-49. https://doi.org/10.1038/nrc.2016.89
18. Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. New England Journal of Medicine. 2012 Nov 8;367(19):1792-802. https://doi.org/10.3390/cancers16071313
19. Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert opinion on drug safety. 2010 Jul 1;9(4):603-21. https://doi.org/10.1517/14740331003662620
20. Sakellakis M, Akinosoglou K, Kostaki A, Spyropoulou D, Koutras A. Statins and risk of breast cancer recurrence. Breast Cancer: Targets and Therapy. 2016 Nov 4:199-205. https://doi.org/10.2147/BCTT.S116694
21. Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert opinion on drug safety. 2010 Jul 1;9(4):603-21. https://doi.org/10.1517/14740331003662620
22. Sakellakis M, Akinosoglou K, Kostaki A, Spyropoulou D, Koutras A. Statins and risk of breast cancer recurrence. Breast Cancer: Targets and Therapy. 2016 Nov 4:199-205. https://doi.org/10.2147/BCTT.S116694
23. Kochuparambil ST, Al-Husein B, Goc A, Soliman S, Somanath PR. Anticancer efficacy of simvastatin on prostate cancer cells and tumor xenografts is associated with inhibition of Akt and reduced prostate-specific antigen expression. Journal of Pharmacology and Experimental Therapeutics. 2011 Feb 1;336(2):496-505. https://doi.org/10.1124/jpet.110.174870
24. Warren CF, Wong-Brown MW, Bowden NA. BCL-2 family isoforms in apoptosis and cancer. Cell death & disease. 2019 Feb 21;10(3):177. https://doi.org/10.1038/s41419-019- 1407-6
25. Cafforio P, Dammacco F, Gernone A, Silvestris F. Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells. Carcinogenesis. 2005 May 1;26(5):883-91. https://doi.org/10.1093/carcin/bgi036
26. Kamigaki M, Sasaki T, Serikawa M, Inoue M, Kobayashi K, Itsuki H, Minami T, Yukutake M, Okazaki A, Ishigaki T, Ishii Y. Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells. International journal of oncology. 2011 Sep 1;39(3):561-8. https://doi.org/10.3892/ijo.2011.1087
27. Hoque A, Chen H, Xu XC. Statin induces apoptosis and cell growth arrest in prostate cancer cells. Cancer Epidemiology Biomarkers & Prevention. 2008 Jan;17(1):88-94. https://doi.org/10.1158/1055-9965.EPI-07-0531
28. Fujiwara D, Tsubaki M, Takeda T, Tomonari Y, Koumoto YI, Sakaguchi K, Nishida S. Statins induce apoptosis through inhibition of Ras signaling pathways and enhancement of Bim and p27 expression in human hematopoietic tumor cells. Tumor Biology. 2017;Oct;39(10):1010428317734947. https://doi.org/10.1177/1010428317734947
29. Goc A, Kochuparambil ST, Al-Husein B, Al-Azayzih A, Mohammad S, Somanath PR. Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis. BMC cancer. 2012 Dec;12:1-3. https://doi.org/10.1186/1471-2407-12-409
30. Thurnher M, Nussbaumer O, Gruenbacher G. Novel aspects of mevalonate pathway inhibitors as antitumor agents. Clinical Cancer Research. 2012 Jul 1;18(13):3524-31. https://doi.org/10.1158/1078-0432.CCR-12-0489
31. Wang G, Cao R, Wang Y, Qian G, Dan HC, Jiang W, Ju L, Wu M, Xiao Y, Wang X. Simvastatin induces cell cycle arrest and inhibits proliferation of bladder cancer cells via PPARγ signalling pathway. Scientific reports. 2016 Oct 25;6(1):35783. https://doi.org/10.1038/srep35783
32. Kamigaki M, Sasaki T, Serikawa M, Inoue M, Kobayashi K, Itsuki H, Minami T, Yukutake M, Okazaki A, Ishigaki T, Ishii Y. Statins induce apoptosis and inhibit proliferation in cholangiocarcinoma cells. International journal of oncology. 2011 Sep 1;39(3):561-8. https://doi.org/10.3892/ijo.2011.1087
33. Matusewicz L, Meissner J, Toporkiewicz M, Sikorski AF. The effect of statins on cancer cells. Tumor Biology. 2015 Jul;36:4889-904. https://doi.org/10.1007/s13277-015-3551-7
34. Wang T, Seah S, Loh X, Chan CW, Hartman M, Goh BC, Lee SC. Simvastatin-induced breast cancer cell death and deactivation of PI3K/Akt and MAPK/ERK signalling are reversed by metabolic products of the mevalonate pathway. Oncotarget. 2015 Nov 11;7(3):2532-44. doi: 10.18632/oncotarget.6304
35. Wang G, Cao R, Wang Y, Qian G, Dan HC, Jiang W, Ju L, Wu M, Xiao Y, Wang X. Simvastatin induces cell cycle arrest and inhibits proliferation of bladder cancer cells via PPARγ signalling pathway. Scientific reports. 2016 Oct 25;6(1):35783. https://doi.org/10.1038/srep35783
36. Kany S, Woschek M, Kneip N, Sturm R, Kalbitz M, Hanschen M, Relja B. Simvastatin exerts anticancer effects in osteosarcoma cell lines via geranylgeranylation and c-Jun activation. International journal of oncology. 2018 Apr 1;52(4):1285-94. https://doi.org/10.3892/ijo.2018.4288
37. Ingersoll MA, Miller DR, Martinez O, Wakefield CB, Hsieh KC, Simha MV, Kao CL, Chen HT, Batra SK, Lin MF. Statin derivatives as therapeutic agents for castration- resistant prostate cancer. Cancer letters. 2016 Dec 1;383(1):94-105. https://doi.org/10.1016/j.canlet.2016.09.008
38. Cho SJ, Kim JS, Kim JM, Lee JY, Jung HC, Song IS. Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis‐associated colon cancer in mice. International journal of cancer. 2008 Aug 15;123(4):951-7. https://doi.org/10.1002/ijc.23593
39. Gash KJ, Chambers AC, Cotton DE, Williams AC, Thomas MG. Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy. British journal of cancer. 2017 Jul;117(2):210-9. https://doi.org/10.1038/bjc.2017.175
40. Cloos J, Peters GJ, Al M, Assaraf YG, Wang L, Singer JW, Cortes JE, Ossenkoppele GJ, Jansen G. Statins Potentiate Aminopeptidase Inhibitor (pro) Drug Activity in Acute Myeloid Leukemia Cells. Blood. 2018 Nov 29;132:3945. https://doi.org/10.1182/blood- 2018-99-114447
41. Cortes J, Feldman E, Yee K, Rizzieri D, Advani AS, Charman A, Spruyt R, Toal M, Kantarjian H. Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): a randomised open-label phase 2 study. The Lancet Oncology. 2013 Apr1;14(4):354-62. https://doi.org/10.1016/S1470-2045(13)70037-8
42. Sahebkar A, Simental‐Mendía LE, Guerrero‐Romero F, Golledge J, Watts GF. Effect of statin therapy on plasma proprotein convertase subtilisin kexin 9 (PCSK9) concentrations: a systematic review and meta‐analysis of clinical trials. Diabetes, Obesity and Metabolism. 2015 Nov;17(11):1042-55. https://doi.org/10.1111/dom.12536
43. Adorni MP, Zimetti F, Lupo MG, Ruscica M, Ferri N. Naturally occurring PCSK9 inhibitors. Nutrients. 2020 May 16;12(5):1440. https://doi.org/10.3390/nu12051440
44. Momtazi-Borojeni AA, Nik ME, Jaafari MR, Banach M, Sahebkar A. Potential anti- tumor effect of a nanoliposomal antiPCSK9 vaccine in mice bearing colorectal cancer. Archives of Medical Science. 2019 May 1;15(3):559-69. https://doi.org/10.5114/aoms.2019.84732
45. Dong Z, Zhang W, Chen S, Liu C. Silibinin A decreases statin-induced PCSK9 expression in human hepatoblastoma HepG2 cells. Molecular medicine reports. 2019 Aug 1;20(2):1383- 92. https://doi.org/10.3892/mmr.2019.10344
46. Środa-Pomianek K, Michalak K, Palko-Łabuz A, Uryga A, Świątek P, Majkowski M, Wesołowska O. The combined use of phenothiazines and statins strongly affects doxorubicin-resistance, apoptosis, and Cox-2 activity in colon cancer cells. International journal of molecular sciences. 2019 Feb 22;20(4):955. https://doi.org/10.3390/ijms20040955
47. Um HD. Bcl-2 family proteins as regulators of cancer cell invasion and metastasis: a review focusing on mitochondrial respiration and reactive oxygen species. Oncotarget. 2016 Feb 2;7(5):5193. doi: 10.18632/oncotarget.6405
48. Beckwitt CH, Clark AM, Ma B, Whaley D, Oltvai ZN, Wells A. Statins attenuate outgrowth of breast cancer metastases. British journal of cancer. 2018 Oct 30;119(9):1094-105. https://doi.org/10.1038/s41416-018-0267-7
49. Göbel A, Rauner M, Hofbauer LC, Rachner TD. Cholesterol and beyond-The role of the mevalonate pathway in cancer biology. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2020 Apr 1;1873(2):188351. https://doi.org/10.1016/j.bbcan.2020.188351
50. Moon SH, Huang CH, Houlihan SL, Regunath K, Freed-Pastor WA, Morris JP, Tschaharganeh DF, Kastenhuber ER, Barsotti AM, Culp-Hill R, Xue W. p53 represses the mevalonate pathway to mediate tumor suppression. Cell. 2019 Jan 24;176(3):564-80. https://doi.org/10.1016/j.cell.2018.11.011
51. Ridley AJ. Rho proteins and cancer. Breast cancer research and treatment. 2004 Mar;84:13- 9. https://doi.org/10.1016/j.cell.2018.11.011
52. Narumiya S, Tanji M, Ishizaki T. Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion. Cancer and Metastasis Reviews. 2009 Jun;28:65-76. https://doi.org/10.1007/s10555-008-9170-7
53. Jones HM, Fang Z, Sun W, Clark LH, Stine JE, Tran AQ, Sullivan SA, Gilliam TP, Zhou C, Bae-Jump VL. Atorvastatin exhibits anti-tumorigenic and anti-metastatic effects in ovarian cancer in vitro. American journal of cancer research. 2017;7(12):2478.
54. Buranrat B, Senggunprai L, Prawan A, Kukongviriyapan V. Simvastatin and atorvastatin as inhibitors of proliferation and inducers of apoptosis in human cholangiocarcinoma cells. Life sciences. 2016 May 15;153:41-9. https://doi.org/10.1016/j.lfs.2016.04.018
55. Stine JE, Guo H, Sheng X, Han X, Schointuch MN, Gilliam TP, Gehrig PA, Zhou C, Bae- Jump VL. The HMG-CoA reductase inhibitor, simvastatin, exhibits anti-metastatic and anti- tumorigenic effects in ovarian cancer. Oncotarget. 2016 Jan 1;7(1):946. doi: 10.18632/oncotarget.5834
56. Georgakopoulos-Soares I, Chartoumpekis DV, Kyriazopoulou V, Zaravinos A. EMT factors and metabolic pathways in cancer. Frontiers in oncology. 2020 Apr 7;10:499. https://doi.org/10.3389/fonc.2020.00499
57. Koohestanimobarhan S, Salami S, Imeni V, Mohammadi Z, Bayat O. Lipophilic statins antagonistically alter the major epithelial‐to‐mesenchymal transition signaling pathways in breast cancer stem–like cells via inhibition of the mevalonate pathway. Journal of cellular biochemistry. 2019 Feb;120(2):2515-31.https://doi.org/10.1002/jcb.27544
58. Fan Z, Jiang H, Wang Z, Qu J. Atorvastatin partially inhibits the epithelial-mesenchymal transition in A549 cells induced by TGF-β1 by attenuating the upregulation of SphK1. Oncology reports. 2016 Aug 1;36(2):1016-22. https://doi.org/10.3892/or.2016.4897
59. Ma Q, Gao Y, Xu P, Li K, Xu X, Gao J, Qi Y, Xu J, Yang Y, Song W, He X. Atorvastatin inhibits breast cancer cells by downregulating PTEN/AKT pathway via promoting ras homolog family member B (RhoB). BioMed research international. 2019 Oct;2019. https://doi.org/10.1155/2019/3235021
60. Soukhtanloo M, Mohtashami E, Maghrouni A, Mollazadeh H, Mousavi SH, Roshan MK, Tabatabaeizadeh SA, Hosseini A, Vahedi MM, Jalili-Nik M, Afshari AR. Natural products as promising targets in glioblastoma multiforme: a focus on NF-κB signaling pathway. Pharmacological reports. 2020 Apr; 72:285-95. https://doi.org/10.1007/s43440-020- 00081-7
61. Afshari AR, Jalili-Nik M, Soukhtanloo M, Ghorbani A, Sadeghnia HR, Mollazadeh H, Roshan MK, Rahmani F, Sabri H, Vahedi MM, Mousavi SH. Auraptene-induced cytotoxicity mechanisms in human malignant glioblastoma (U87) cells: role of reactive oxygen species (ROS). EXCLI journal. 2019;18:576. doi: 10.17179/excli2019-1136
62. Göbel A, Rauner M, Hofbauer LC, Rachner TD. Cholesterol and beyond-The role of the mevalonate pathway in cancer biology. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2020 Apr 1;1873(2):188351. https://doi.org/10.1016/j.bbcan.2020.188351
63. Yanae M, Tsubaki M, Satou T, Itoh T, Imano M, Yamazoe Y, Nishida S. Statin-induced apoptosis via the suppression of ERK1/2 and Akt activation by inhibition of the geranylgeranyl-pyrophosphate biosynthesis in glioblastoma. Journal of Experimental & Clinical Cancer Research. 2011 Dec;30(1):1-8. https://doi.org/10.1186/1756-9966-30-74
64. Cai WY, Zhuang Y, Yan F, Li T, Song WT, Sun JH. Effect of survivin downregulation by simvastatin on the growth and invasion of salivary adenoid cystic carcinoma . Molecular medicine reports . 2018 Aug 1;18(2):1939-46. https://doi.org/10.3892/mmr.2018.9204
65. Shojaei S, Alizadeh J, Thliveris J, Koleini N, Kardami E, Hatch GM, Xu F, Hombach- Klonisch S, Klonisch T, Ghavami S. Statins: a new approach to combat temozolomide chemoresistance in glioblastoma. Journal of Investigative Medicine. 2018 Dec;66(8):1083- 7. https://doi.org/10.1136/jim-2018-000874
66. Peng P, Wei W, Long C, Li J. Atorvastatin augments temozolomide's efficacy in glioblastoma via prenylation-dependent inhibition of Ras signaling. Biochemical and biophysical research communications. 2017 Jul 29;489(3):293-8. https://doi.org/10.1016/j.bbrc.2017.05.147
67. Bhavsar S, Hagan K, Arunkumar R, Potylchansky Y, Grasu R, Dang A, Carlson R, Cowels C, Arnold B, Rahlfs TF, Lipski I. Preoperative statin use is not associated with improvement in survival after glioblastoma surgery. Journal of Clinical Neuroscience. 2016 Sep 1; 31:176-80. https://doi.org/10.1016/j.jocn.2016.03.010
68. Gupta A, Stokes W, Eguchi M, Hararah M, Amini A, Mueller A, Morgan R, Bradley C, Raben D, McDermott J, Karam SD. Statin use associated with improved overall and cancer specific survival in patients with head and neck cancer. Oral oncology. 2019 Mar 1;90:54- 66. https://doi.org/10.1016/j.oraloncology.2019.01.019
69. Fritz G, Henninger C, Huelsenbeck J. Potential use of HMG-CoA reductase inhibitors (statins) as radioprotective agents. British medical bulletin . 2011 Mar 1;97(1):17-26. https://doi.org/10.1093/bmb/ldq044
70. Weis M, Heeschen C, Glassford AJ, Cooke JP. Statins have biphasic effects on angiogenesis. Circulation. 2002 Feb 12;105(6):739-45. https://doi.org/10.1161/hc0602.103393
71. Dulak J, Józkowicz A. Anti-angiogenic and anti-inflammatory effects of statins: relevance to anti-cancer therapy. Current cancer drug targets. 2005 Dec 1;5(8):579-94. https://doi.org/10.2174/156800905774932824
72. Björkhem-Bergman L, Lindh JD, Bergman P. What is a relevant statin concentration in cell experiments claiming pleiotropic effects. British journal of clinical pharmacology. 2011 Jul;72(1):164. doi: 10.1111/j.1365-2125.2011.03907.x
73. Peng P, Wei W, Long C, Li J. Atorvastatin augments temozolomide's efficacy in glioblastoma via prenylation-dependent inhibition of Ras signaling. Biochemical and biophysical research communications. 2017 Jul 29;489(3):293-8. https://doi.org/10.1016/j.bbrc.2017.05.147
74. Yamamoto Y, Tomiyama A, Sasaki N, Yamaguchi H, Shirakihara T, Nakashima K, Kumagai K, Takeuchi S, Toyooka T, Otani N, Wada K. Intracellular cholesterol level regulates sensitivity of glioblastoma cells against temozolomide-induced cell death by modulation of caspase-8 activation via death receptor 5-accumulation and activation in the plasma membrane lipid raft. Biochemical and biophysical research communications . 2018 Jan 1;495(1):1292-9.https://doi.org/10.1016/j.bbrc.2017.11.113
75. Zhu Z, Zhang P, Li N, Kiang KM, Cheng SY, Wong VK, Leung GK. Lovastatin enhances cytotoxicity of temozolomide via impairing autophagic flux in glioblastoma cells. BioMed research international. 2019;2019. https://doi.org/10.1155/2019/2710693
76. Rodriguez GE, Blankstein A, Henson ES, Gibson SB. 18th BIENNIAL CANADIAN NEURO-ONCOLOGY MEETING| Banff Alberta| May 10-12, 2018 _. doi:10.1017/cjn.2018.280
77. Shojaei S, Koleini N, Samiei E, Aghaei M, Cole LK, Alizadeh J, Islam MI, Vosoughi AR, Albokashy M, Butterfield Y, Marzban H. Simvastatin increases temozolomide‐induced cell death by targeting the fusion of autophagosomes and lysosomes. The FEBS journal. 2020 Mar;287(5):1005-34..
78. Oliveira KA, Dal-Cim T, Lopes FG, Ludka FK, Nedel CB, Tasca CI. Atorvastatin promotes cytotoxicity and reduces migration and proliferation of human A172 glioma cells. Molecular neurobiology. 2018 Feb;55:1509-23. https://doi.org/10.1007/s12035-017-0423-8
79. Misirkic M, Janjetovic K, Vucicevic L, Tovilovic G, Ristic B, Vilimanovich U, Harhaji- Trajkovic L, Sumarac-Dumanovic M, Micic D, Bumbasirevic V, Trajkovic V. Inhibition of AMPK-dependent autophagy enhances in vitro antiglioma effect of simvastatin. Pharmacological research. 2012 Jan 1;65(1):111-9. https://doi.org/10.1016/j.phrs.2011.08.003
80. Chan DY, Chen GG, Poon WS, Liu PC. Lovastatin sensitized human glioblastoma cells to TRAIL-induced apoptosis. Journal of neuro-oncology. 2008 Feb;86:273-83. https://doi.org/10.1007/s11060-007-9475-3
81. Liu Y, Chen L, Gong Z, Shen L, Kao C, Hock JM, Sun L, Li X. Lovastatin enhances adenovirus-mediated TRAIL induced apoptosis by depleting cholesterol of lipid rafts and affecting CAR and death receptor expression of prostate cancer cells. Oncotarget. 2015 Feb;6(5):3055. Doi: 10.18632/oncotarget.3073
82. Zhu Z, Zhang P, Li N, Kiang KM, Cheng SY, Wong VK, Leung GK. Lovastatin enhances cytotoxicity of temozolomide via impairing autophagic flux in glioblastoma cells. BioMed research international. 2019;2019. https://doi.org/10.1155/2019/2710693
83. Bayat N, Ebrahimi-Barough S, Norouzi-Javidan A, Saberi H, Tajerian R, Ardakan MM, Shirian S, Ai A, Ai J. Apoptotic effect of atorvastatin in glioblastoma spheroids tumor cultured in fibrin gel. Biomedicine & Pharmacotherapy. 2016 Dec 1;84:1959-66. https://doi.org/10.1016/j.biopha.2016.11.003
84. Bayat N, Ebrahimi-Barough S, Norouzi-Javidan A, Saberi H, Tajerian R, Ardakan MM, Shirian S, Ai A, Ai J. Apoptotic effect of atorvastatin in glioblastoma spheroids tumor cultured in fibrin gel. Biomedicine & Pharmacotherapy. 2016 Dec 1;84:1959-66. https://doi.org/10.1016/j.biopha.2016.11.003
85. Wawruszak A, Kalafut J, Okon E, Czapinski J, Halasa M, Przybyszewska A, Miziak P, Okla K, Rivero-Muller A, Stepulak A. Histone deacetylase inhibitors and phenotypical transformation of cancer cells. Cancers. 2019 Jan 27;11(2):148. DOI: 10.3390/cancers11020148
86. Ediriweera MK, Tennekoon KH, Samarakoon SR. Emerging role of histone deacetylase inhibitors as anti-breast-cancer agents. Drug discovery today. 2019 Mar 1;24(3):685-702. https://doi.org/10.1016/j.drudis.2019.02.003
87. Chang YL, Huang LC, Chen YC, Wang YW, Hueng DY, Huang SM. The synergistic effects of valproic acid and fluvastatin on apoptosis induction in glioblastoma multiforme cell lines. The international journal of biochemistry & cell biology. 2017 Nov 1;92:155- 63. https://doi.org/10.1016/j.biocel.2017.10.003
88. Jiang Z, Zheng X, Lytle RA, Higashikubo R, Rich KM. Lovastatin‐induced up‐regulation of the BH3‐only protein, Bim, and cell death in glioblastoma cells. Journal of neurochemistry. 2004 Apr;89(1):168-78. https://doi.org/10.1111/j.1471-4159.2004.02319.x
89. Koyuturk M, Ersoz M, Altiok N. Simvastatin induces proliferation inhibition and apoptosis in C6 glioma cells via c-jun N-terminal kinase. Neuroscience letters. 2004 Nov 11;370(2- 3):212-7. https://doi.org/10.1016/j.neulet.2004.08.020
90. Wu H, Jiang H, Lu D, Xiong Y, Qu C, Zhao D, Mahmood A, Chopp M. Effect of simvastatin on glioma cell proliferation, migration and apoptosis. Neurosurgery. 2009 Dec;65(6):1087. DOI: 10.1227/01.NEU.0000360130.52812.1D
91. Qiu Z, Yuan W, Chen T, Zhou C, Liu C, Huang Y, Han D, Huang Q. HMGCR positively regulated the growth and migration of glioblastoma cells. Gene. 2016 Jan 15;576(1):22-7. https://doi.org/10.1016/j.gene.2015.09.067
92. Gliemroth J, Zulewski H, Arnold H, Terzis AJ. Migration, proliferation, and invasion of human glioma cells following treatment with simvastatin. Neurosurgical review. 2003 May;26:117-24. https://doi.org/10.1007/s10143-003-0258-9
93. Fromigué O, Hamidouche Z, Marie PJ. Blockade of the RhoA-JNK-c-Jun-MMP2 cascade by atorvastatin reduces osteosarcoma cell invasion. Journal of Biological Chemistry. 2008 Nov 7;283(45):30549-56. https://doi.org/10.1074/jbc.M801436200
94. Mahajan N, Dhawan V. Inhibition of C-reactive protein induced expression of matrix metalloproteinases by atorvastatin in THP-1 cells. Molecular and cellular biochemistry. 2010 May; 338:77-86. https://doi.org/10.1007/s11010-009-0340-x
95. Sławińska-Brych A, Zdzisińska B, Kandefer-Szerszeń M. Fluvastatin inhibits growth and alters the malignant phenotype of the C6 glioma cell line. Pharmacological Reports. 2014 Feb 1;66(1):121-9.https://doi.org/10.1016/j.pharep.2014.01.002
96. Yongjun Y, Shuyun H, Lei C, Xiangrong C, Zhilin Y, Yiquan K. Atorvastatin suppresses glioma invasion and migration by reducing microglial MT1-MMP expression. Journal of neuroimmunology. 2013 Jul15;260(1-2):1- 8. https://doi.org/10.1016/j.jneuroim.2013.04.020
97. Rajshankar D, Wang B, Worndl E, Menezes S, Wang Y, McCulloch CA. Focal adhesion kinase regulates tractional collagen remodeling, matrix metalloproteinase expression, and collagen structure, which in turn affects matrix‐induced signaling. Journal of cellular physiology. 2020 Mar;235(3):3096-111.https://doi.org/10.1002/jcp.29215
98. Deng B, Liu R, Tian X, Han Z, Chen J. Simulated microgravity inhibits the viability and migration of glioma via FAK/RhoA/Rock and FAK/Nek2 signaling. In Vitro Cellular & Developmental Biology-Animal. 2019 Apr 15;55:260-71.https://doi.org/10.1007/s11626- 019-00334-7
99. Barańska J, editor. Glioma signaling. Springer; 2013.
100. Obara S, Nakata M, Takeshima H, Kuratsu JI, Maruyama I, Kitajima I. Inhibition of migration of human glioblastoma cells by cerivastatin in association with focal adhesion kinase (FAK). Cancer letters. 2002 Nov 28;185(2):153-61.https://doi.org/10.1016/S0304- 3835(02)00278-1
101. Tsubaki M, Yamazoe Y, Yanae M, Satou T, Itoh T, Kaneko J, Kidera Y, Moriyama K, Nishida S. Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-β as angiogenic factors in mouse osteosarcoma. Cytokine. 2011 Apr 1;54(1):100- 7.https://doi.org/10.1016/j.cyto.2011.01.005
102. Xiao A, Brenneman B, Floyd D, Comeau L, Spurio K, Olmez I, Lee J, Nakano I, Godlewski J, Bronisz A, Kagaya N. Statins affect human glioblastoma and other cancers through TGF-β inhibition. Oncotarget. 2019 Mar 3;10(18):1716. https://doi.org/10.18632%2Foncotarget.26733
103. Bayat N, Izadpanah R, Ebrahimi-Barough S, Javidan AN, Ai A, Ardakan MM, Saberi H, Ai J. The anti-angiogenic effect of atorvastatin in glioblastoma spheroids tumor cultured in fibrin gel: in 3D in vitro model. Asian Pacific journal of cancer prevention: APJCP. 2018;19(9):2553. https://doi.org/10.22034%2FAPJCP.2018.19.9.2553
104. Bababeygy SR, Polevaya NV, Youssef S, Sun A, Xiong A, Prugpichailers T, Veeravagu A, Hou LC, Steinman L, Tse V. HMG-CoA reductase inhibition causes increased necrosis and apoptosis in an in vivo mouse glioblastoma multiforme model. Anticancer research. 2009 Dec 1;29(12):4901-8.
105. Jakobisiak M, Golab J. Potential antitumor effects of statins. International journal of oncology. 2003 Oct 1;23(4):1055-69. https://doi.org/10.3892/ijo.23.4.1055
106. Afshordel S, Kern B, Clasohm J, König H, Priester M, Weissenberger J, Kögel D, Eckert GP. Lovastatin and perillyl alcohol inhibit glioma cell invasion, migration, and proliferation–impact of Ras-/Rho-prenylation. Pharmacological research. 2015 Jan 1;91:69-77. https://doi.org/10.1016/j.phrs.2014.11.006
107. Yarmolinsky J, Bull CJ, Vincent EE, Robinson J, Walther A, Smith GD, Lewis SJ, Relton CL, Martin RM. Association between genetically proxied inhibition of HMG- CoA reductase and epithelial ovarian cancer. Jama. 2020 Feb 18;323(7):646- 55.doi:10.1001/jama.2020.0150
108. Tamburrino D, Crippa S, Partelli S, Archibugi L, Arcidiacono PG, Falconi M, Capurso G. Statin use improves survival in patients with pancreatic ductal adenocarcinoma: A meta- analysis. Digestive and Liver Disease. 2020 Apr 1;52(4):392-9. https://doi.org/10.1016/j.dld.2020.01.008
109. Iarrobino NA, Gill B, Bernard ME, Mishra MV, Champ CE. Targeting tumor metabolism with statins during treatment for advanced-stage pancreatic cancer. American journal of clinical oncology. 2018 Nov;41(11):1125.DOI: 10.1097/COC.0000000000000433
110. Lin JJ, Ezer N, Sigel K, Mhango G, Wisnivesky JP. The effect of statins on survival in patients with stage IV lung cancer. Lung cancer. 2016 Sep 1;99:137-42. https://doi.org/10.1016/j.lungcan.2016.07.006
111. Omori M, Okuma Y, Hakozaki T, Hosomi Y. Statins improve survival in patients previously treated with nivolumab for advanced non-small cell lung cancer: An observational study. Molecular and clinical oncology. 2019 Jan 1;10(1):137-43. https://doi.org/10.3892/mco.2018.1765
112. Larner J, Jane J, Laws E, Packer R, Myers C, Shaffrey M. A phase I-II trial of lovastatin for anaplastic astrocytoma and glioblastoma multiforme. American journal of clinical oncology. 1998 Dec 1;21(6):579-83.
113. Ferris JS, McCoy L, Neugut AI, Wrensch M, Lai R. HMG CoA reductase inhibitors, NSAIDs and risk of glioma. International journal of cancer. 2012 Sep 15;131(6):E1031-7. https://doi.org/10.1002/ijc.27536
114. Chen BK, Chiu HF, Yang CY. Statins are Associated With a Reduced Risk of Brain Cancer: A Population-Based Case–Control Study. Medicine. 2016 Apr;95(17). https://doi.org/10.1097/MD.0000000000003392
115. Vuletic S, Riekse RG, Marcovina SM, Peskind ER, Hazzard WR, Albers JJ. Statins of different brain penetrability differentially affect CSF PLTP activity. Dementia and geriatric cognitive disorders. 2006;22(5-6):392-8.https://doi.org/10.1159/000095679
116. Jiang Z, Zheng X, Lytle RA, Higashikubo R, Rich KM. Lovastatin‐induced up‐regulation of the BH3‐only protein, Bim, and cell death in glioblastoma cells. Journal of neurochemistry. 2004 Apr;89(1):168-78.https://doi.org/10.1111/j.1471- 4159.2004.02319.x
117. Seliger C, Schaertl J, Gerken M, Luber C, Proescholdt M, Riemenschneider MJ, Leitzmann MF, Hau P, Klinkhammer-Schalke M. Use of statins or NSAIDs and survival of patients with high-grade glioma. PloS one. 2018 Dec 3;13(12):e0207858.https://doi.org/10.1371/journal.pone.0207858
118. Seliger C, Meier CR, Becker C, Jick SS, Bogdahn U, Hau P, Leitzmann MF. Statin use and risk of glioma: population-based case–control analysis. European journal of epidemiology. 2016 Sep;31:947-52.https://doi.org/10.1007/s10654-016-0145-7
119. Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, Blumenthal R, Danesh J, Smith GD, DeMets D, Evans S. Interpretation of the evidence for the efficacy and safety of statin therapy. The Lancet. 2016 Nov 19;388(10059):2532-61. https://doi.org/10.1016/S0140-6736(16)31357-5
120. Ibrahim AB, Zaki HF, Ibrahim WW, Omran MM, Shouman SA. Evaluation of tamoxifen and simvastatin as the combination therapy for the treatment of hormonal dependent breast cancer cells. Toxicology Reports. 2019 Jan 1;6:1114- 26.https://doi.org/10.1016/j.toxrep.2019.10.016
121. Środa-Pomianek K, Michalak K, Palko-Łabuz A, Uryga A, Szczęśniak-Sięga B, Wesołowska O. Simvastatin strongly augments proapoptotic, anti-inflammatory and cytotoxic activity of oxicam derivatives in doxorubicin-resistant colon cancer cells. Anticancer research. 2019 Feb 1;39(2):727-34DOI: https://doi.org/10.21873/anticanres.13169
122. Xia K, Zhang P, Hu J, Hou H, Xiong M, Xiong J, Yan N. Synergistic effect of receptor-interacting protein 140 and simvastatin on the inhibition of proliferation and survival of hepatocellular carcinoma cells. Oncology letters. 2018 Apr 1;15(4):4344-50. https://doi.org/10.3892/ol.2018.7831
123. Fahmy UA, Aljaeid BM. Combined strategy for suppressing breast carcinoma MCF- 7 cell lines by loading simvastatin on alpha lipoic acid nanoparticles. Expert opinion on drug delivery. 2016 Dec 1;13(12):1653- 60.https://doi.org/10.1080/17425247.2016.1236788
124. Wu X, Song M, Qiu P, Rakariyatham K, Li F, Gao Z, Cai X, Wang M, Xu F, Zheng J, Xiao H. Synergistic chemopreventive effects of nobiletin and atorvastatin on colon carcinogenesis. Carcinogenesis. 2017 Apr 1;38(4):455- 64. https://doi.org/10.1093/carcin/bgx018
125. Li N, Xie X, Hu Y, He H, Fu X, Fang T, Li C. Herceptin-conjugated liposomes co- loaded with doxorubicin and simvastatin in targeted prostate cancer therapy. American journal of translational research. 2019;11(3):1255.
126. Peng M, Darko KO, Tao T, Huang Y, Su Q, He C, Yin T, Liu Z, Yang X. Combination of metformin with chemotherapeutic drugs via different molecular mechanisms. Cancer treatment reviews. 2017 Mar 1;54:24- 33.https://doi.org/10.1016/j.ctrv.2017.01.005
127. Kim JS, Turbov J, Rosales R, Thaete LG, Rodriguez GC. Combination simvastatin and metformin synergistically inhibits endometrial cancer cell growth. Gynecologic oncology. 2019 Aug 1;154(2):432-40.https://doi.org/10.1016/j.ygyno.2019.05.022
128. Wang ZS, Huang HR, Zhang LY, Kim S, He Y, Li DL, Farischon C, Zhang K, Zheng X, Du ZY, Goodin S. Mechanistic study of inhibitory effects of metformin and atorvastatin in combination on prostate cancer cells in vitro and in vivo. Biological and Pharmaceutical Bulletin. 2017 Aug 1;40(8):1247-54. https://doi.org/10.1248/bpb.b17-00077
129. Lu SE, Lin Y, Graber JM, Rotter D, Zhang L, Petersen GM, Demissie K, Lu-Yao G, Tan XL. Differential and joint effects of metformin and statins on overall survival of elderly patients with pancreatic adenocarcinoma: a large population-based study. Cancer Epidemiology, Biomarkers & Prevention. 2017 Aug 1;26(8):1225- 32.https://doi.org/10.1158/1055-9965.EPI-17-0227
130. Gehrke T, Scherzad A, Hackenberg S, Ickrath P, Schendzielorz P, Hagen R, Kleinsasser N. Additive antitumor effects of celecoxib and simvastatin on head and neck squamous cell carcinoma in vitro. International journal of oncology. 2017 Sep 1;51(3):931- 8.https://doi.org/10.3892/ijo.2017.4071
131. Buranrat B, Suwannaloet W, Naowaboot J. Simvastatin potentiates doxorubicin activity against MCF-7 breast cancer cells. Oncology letters. 2017 Nov 1;14(5):6243-50. https://doi.org/10.3892/ol.2017.6783
132. Jouve JL, Lecomte T, Bouché O, Barbier E, Akouz FK, Riachi G, Khac EN, Ollivier- Hourmand I, Debette-Gratien M, Faroux R, Villing AL. Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma. Journal of hepatology. 2019 Sep 1;71(3):516-22.https://doi.org/10.1016/j.jhep.2019.04.021
133. Chen YH, Chen YC, Lin CC, Hsieh YP, Hsu CS, Hsieh MC. Synergistic anticancer effects of gemcitabine Cancer management and research. 2020; 12:4645. https://doi.org/10.2147/CMAR.S247876
Crossmark
Statistics
99 Views | 24 Downloads
How to Cite
1.
JAYBHAYE AG, Nikam SS, KAYANDE KP, PATIL PM, SUROSHE AV, ZALTE PB, BHUJBAL SA. Statins as a Combatant for Treatment of Glioblastoma. JDDT [Internet]. 15Jun.2024 [cited 17Jul.2024];14(6):237-46. Available from: https://jddtonline.info/index.php/jddt/article/view/6624