2,050
Views
1
CrossRef citations to date
0
Altmetric
Research Paper

Dichloroacetic acid (DCA) synergizes with the SIRT2 inhibitor Sirtinol and AGK2 to enhance anti-tumor efficacy in non-small cell lung cancer

, , , & ORCID Icon
Pages 835-846 | Received 22 Dec 2017, Accepted 20 May 2018, Published online: 01 Aug 2018

References

  • Imai S, Armstrong CM, Kaeberlein M. Guarente L Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403(6771):795–800. doi:10.1038/35001622.
  • Wang Yp, Zhou Ls, Zhao Yz, Wang Sw, Chen Ll, Liu Lx, Ling Zq, Hu Fj, Sun Yp, Zhang Jy et al. Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. EMBO J. 2014;33(12):1304–1320. doi:10.1002/embj.201387224.
  • Xu Y, Li F, Lv L, Li T, Zhou X, Deng CX, Guan KL, Lei QY. Xiong Y Oxidative stress activates SIRT2 to deacetylate and stimulate phosphoglycerate mutase. Cancer Res. 2014;74(13):3630–3642. doi:10.1158/0008-5472.CAN-13-3615.
  • Wang F, Nguyen M, Qin FX. Tong Q SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction. Aging Cell. 2007;6(4):505–514. doi:10.1111/j.1474-9726.2007.00304.x.
  • Zhao D, Zou SW, Liu Y, Zhou X, Mo Y, Wang P, Xu YH, Dong B, Xiong Y, Lei QY, et al. Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell. 2013;23(4):464–476. doi:10.1016/j.ccr.2013.02.005.
  • Rumpf T, Schiedel M, Karaman B, Roessler C, North BJ, Lehotzky A, Olah J, Ladwein KI, Schmidtkunz K, Gajer M, et al. 2015; Selective Sirt2 inhibition by ligand-induced rearrangement of the active site. Nat Commun. 6:6263. doi:10.1038/ncomms7263.
  • Jing H, Hu J, He B, Negron Abril YL, Stupinski J, Weiser K, Carbonaro M, Chiang YL, Southard T, Giannakakou P, et al. A SIRT2-Selective inhibitor promotes c-Myc oncoprotein degradation and exhibits broad anticancer activity. Cancer Cell. 2016;29(5):767–768. doi:10.1016/j.ccell.2016.04.005.
  • Grozinger CM, Chao ED, Blackwell HE, Moazed D. Schreiber Sl Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening. J Biol Chem. 2001;276(42):38837–38843. doi:10.1074/jbc.M106779200.
  • Outeiro TF, Kontopoulos E, Altmann SM, Kufareva I, Strathearn KE, Amore AM, Volk CB, Maxwell MM, Rochet JC, McLean PJ, et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson’s disease. Science. 2007;317(5837):516–519. doi:10.1126/science.1143780.
  • Cheon MG, Kim W, Choi M, Je: Ak-1 K. a specific SIRT2 inhibitor, induces cell cycle arrest by downregulating Snail in HCT116 human colon carcinoma cells. Cancer Lett. 2015;356(2 Pt B):637–645. doi:10.1016/j.canlet.2014.10.012.
  • Zhao D, Mo Y, Li MT, Zou SW, Cheng ZL, Sun YP, Xiong Y, Guan KL, Qy L. NOTCH-induced aldehyde dehydrogenase 1A1 deacetylation promotes breast cancer stem cells. J Clin Invest. 2014;124(12):5453–5465. doi:10.1172/JCI76611.
  • Singh S, Kumar PU, Thakur S, Kiran S, Sen B, Sharma S, Rao VV, Poongothai AR. Ramakrishna G Expression/localization patterns of sirtuins (SIRT1, SIRT2, and SIRT7) during progression of cervical cancer and effects of sirtuin inhibitors on growth of cervical cancer cells. Tumour Biol. 2015;36(8):6159–6171. doi:10.1007/s13277-015-3300-y.
  • Wang J, Kim TH, Ahn MY, Lee J, Jung JH, Choi WS, Lee BM, Yoon KS, Yoon S. Kim HS: sirtinol, a class III HDAC inhibitor, induces apoptotic and autophagic cell death in MCF-7 human breast cancer cells. Int J Oncol. 2012;41(3):1101–1109. doi:10.3892/ijo.2012.1534.
  • Peck B, Chen CY, Ho KK, Di Fruscia P, Myatt SS, Coombes RC, Fuchter MJ, Hsiao CD. Lam Ew SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol Cancer Ther. 2010;9(4):844–855. doi:10.1158/1535-7163.MCT-09-0971.
  • Ota H, Tokunaga E, Chang K, Hikasa M, Iijima K, Eto M, Kozaki K, Akishita M, Ouchi Y. Kaneki M Sirt1 inhibitor, Sirtinol, induces senescence-like growth arrest with attenuated Ras-MAPK signaling in human cancer cells. Oncogene. 2006;25(2):176–185. doi:10.1038/sj.onc.1209049.
  • Jin KL, Park JY, Noh EJ, Hoe KL, Lee JH, Kim JH. Nam Jh The effect of combined treatment with cisplatin and histone deacetylase inhibitors on HeLa cells. J Gynecol Oncol. 2010;21(4):262–268. doi:10.3802/jgo.2010.21.4.262.
  • Luthi-Carter R, Taylor DM, Pallos J, Lambert E, Amore A, Parker A, Moffitt H, Smith DL, Runne H, Gokce O, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci U S A. 2010;107(17):7927–7932. doi:10.1073/pnas.1002924107.
  • Kim HW, Kim SA. Ahn Sg Sirtuin inhibitors, EX527 and AGK2, suppress cell migration by inhibiting HSF1 protein stability. Oncol Rep. 2016;35(1):235–242. doi:10.3892/or.2015.4381.
  • He X, Nie H, Hong Y, Sheng C, Xia W. Ying W SIRT2 activity is required for the survival of C6 glioma cells. Biochem Biophys Res Commun. 2012;417(1):468–472. doi:10.1016/j.bbrc.2011.11.141.
  • Webster RM. Combination therapies in oncology. Nat Rev Drug Discov. 2016;15(2):81–82. doi:10.1038/nrd.2016.3.
  • Grbesa I, Pajares MJ, Martinez-Terroba E, Agorreta J, Mikecin AM, Larrayoz M, Idoate MA, Gall-Troselj K, Pio R. Montuenga Lm Expression of sirtuin 1 and 2 is associated with poor prognosis in non-small cell lung cancer patients. PLoS One. 2015;10(4):e0124670. doi:10.1371/journal.pone.0124670.
  • Matsushita N, Takami Y, Kimura M, Tachiiri S, Ishiai M, Nakayama T. Takata M Role of NAD-dependent deacetylases SIRT1 and SIRT2 in radiation and cisplatin-induced cell death in vertebrate cells. Genes Cells. 2005;10(4):321–332. doi:10.1111/j.1365-2443.2005.00836.x.
  • Hoffmann G, Breitenbucher F, Schuler M. Ehrenhofer-Murray Ae A novel sirtuin 2 (SIRT2) inhibitor with p53-dependent pro-apoptotic activity in non-small cell lung cancer. J Biol Chem. 2014;289(8):5208–5216. doi:10.1074/jbc.M113.487736.
  • Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006;58(3):621–681. doi:10.1124/pr.58.3.10.
  • Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70(2):440–446. doi:10.1158/0008-5472.CAN-09-1947.
  • Vander Heiden MG, Cantley LC. Thompson Cb Understanding the warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–1033. doi:10.1126/science.1160809.
  • Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Harry G, et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell. 2007;11(1):37–51. doi:10.1016/j.ccr.2006.10.020.
  • Jia J, Zhu F, Ma X, Cao Z, Li Y. Chen Yz Mechanisms of drug combinations: interaction and network perspectives. Nat Rev Drug Discov. 2009;8(2):111–128. doi:10.1038/nrd2683.
  • Linn TC, Pettit FH. Reed Lj Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc Natl Acad Sci U S A. 1969;62(1):234–241.
  • Jing E, O’Neill BT, Rardin MJ, Kleinridders A, Ilkeyeva OR, Ussar S, Bain JR, Lee KY, Verdin EM, Newgard CB, et al. Sirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation. Diabetes. 2013;62(10):3404–3417. doi:10.2337/db12-1650.
  • Faubert B, Boily G, Izreig S, Griss T, Samborska B, Dong Z, Dupuy F, Chambers C, Fuerth BJ, Viollet B, et al. AMPK is a negative regulator of the warburg effect and suppresses tumor growth in vivo. Cell Metab. 2013;17(1):113–124. doi:10.1016/j.cmet.2012.12.001.
  • Mungai PT, Waypa GB, Jairaman A, Prakriya M, Dokic D, Ball MK. Schumacker Pt Hypoxia triggers AMPK activation through reactive oxygen species-mediated activation of calcium release-activated calcium channels. Mol Cell Biol. 2011;31(17):3531–3545. doi:10.1128/MCB.05124-11.
  • Gomes P, Outeiro TF. Cavadas C Emerging role of sirtuin 2 in the regulation of mammalian metabolism. Trends Pharmacol Sci. 2015;36(11):756–768. doi:10.1016/j.tips.2015.08.001.
  • Park SH, Ozden O, Liu G, Song HY, Zhu Y, Yan Y, Zou X, Kang HJ, Jiang H, Principe DR, et al. SIRT2-mediated deacetylation and tetramerization of pyruvate kinase directs glycolysis and tumor growth. Cancer Res. 2016;76(13):3802–3812. doi:10.1158/0008-5472.CAN-15-2498.
  • Cha Y, Han MJ, Cha HJ, Zoldan J, Burkart A, Jung JH, Jang Y, Kim CH, Jeong HC, Kim BG, et al. Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c-SIRT2 axis. Nat Cell Biol. 2017;19(5):445–456. doi:10.1038/ncb3517.
  • Tsusaka T, Guo T, Yagura T, Inoue T, Yokode M, Inagaki N. Kondoh H Deacetylation of phosphoglycerate mutase in its distinct central region by SIRT2 down-regulates its enzymatic activity. Genes Cells. 2014;19(10):766–777. doi:10.1111/gtc.12176.
  • Fan J, Shan C, Kang HB, Elf S, Xie J, Tucker M, Gu TL, Aguiar M, Lonning S, Chen H, et al. Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex. Mol Cell. 2014;53(4):534–548. doi:10.1016/j.molcel.2013.12.026.
  • Kim I. He Yy 2013; Targeting the AMP-activated protein kinase for cancer prevention and therapy. Front Oncol. 3:175. doi:10.3389/fonc.2013.00175.
  • Dugan LL, You YH, Ali SS, Diamond-Stanic M, Miyamoto S, DeCleves AE, Andreyev A, Quach T, Ly S, Shekhtman G, et al. AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest. 2013;123(11):4888–4899. doi:10.1172/JCI66218.
  • Imamura K, Ogura T, Kishimoto A, Kaminishi M, Esumi H. Cell cycle regulation via p53 phosphorylation by a 5ʹ-AMP activated protein kinase activator, 5-aminoimidazole- 4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line. Biochem Biophys Res Commun. 2001;287(2):562–567. doi:10.1006/bbrc.2001.5627.
  • Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ, Cb T. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell. 2005;18(3):283–293. doi:10.1016/j.molcel.2005.03.027.
  • Liang J, Shao Sh, Xu Zx, Hennessy B, Ding Z, Larrea M, Kondo S, Dumont Dj, Gutterman Ju, Walker Cl et al. The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis. Nat Cell Biol. 2007;9(2):218–224. doi:10.1038/ncb1537.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.