New agents that target senescent cells: The flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463

Aging

Volumn 9, Issue 3, 2017, Pages 955-963

  Zhu, Yi ^a   Doornebal, Ewald J ^a,b   Pirtskhalava, Tamar ^a   Giorgadze, Nino ^a   Wentworth, Mark ^a   Fuhrmann Stroissnigg, Heike ^c   Niedernhofer, Laura J ^c   Robbins, Paul D ^c   Tchkonia, Tamara ^a   Kirkland, James L ^a  

^a MAYO CLINIC   (United States)

^b UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

^c SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Adipose derived stem cells; Aging; Apoptosis; BCL XL inhibitors; Flavonoids; Preadipocytes; Senolytics

Indexed keywords

ANILINE DERIVATIVE; ANTINEOPLASTIC AGENT; BCL2L1 PROTEIN, HUMAN; FISETIN; FLAVONOID; NAVITOCLAX; PROTEIN BCL X; SULFONAMIDE;

ANTAGONISTS AND INHIBITORS; APOPTOSIS; CELL AGING; CELL LINE; CELL SURVIVAL; DRUG EFFECT; HUMAN;

ANILINE COMPOUNDS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BCL-X PROTEIN; CELL LINE; CELL SURVIVAL; CELLULAR SENESCENCE; FLAVONOIDS; HUMANS; SULFONAMIDES;

EID: 85016619121     PISSN: 19454589     EISSN: None     Source Type: Journal    
DOI: 10.18632/aging.101202     Document Type: Article

References (37)

1. Kirkland JL, Tchkonia T. Clinical strategies and animal models for developing senolytic agents. Exp Gerontol. 2015; 68:19-25. doi: 10.1016/j.exger.2014.10.012
2. Zhu Y, Armstrong JL, Tchkonia T, Kirkland JL. Cellular senescence and the senescent secretory phenotype in age-related chronic diseases. Curr Opin Clin Nutr Metab Care. 2014; 17:324-28. doi: 10.1097/MCO.0000000000000065
3. Coppé JP, Patil CK, Rodier F, Sun Y, Muñoz DP, Goldstein J, Nelson PS, Desprez PY, Campisi J. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008; 6:2853-68 doi: 10.1371/journal.pbio.0060301
4. Xu M, Bradley EW, Weivoda MM, Hwang SM, Pirtskhalava T, Decklever T, Curran GL, Ogrodnik M, Jurk D, Johnson KO, Lowe V, Tchkonia T, Westendorf JJ, Kirkland JL. Transplanted senescent cells induce an osteoarthritis-like condition in mice. J Gerontol A Biol Sci Med Sci. 2016glw154. doi: 10.1093/gerona/glw154
5. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL, van Deursen JM. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011; 479:232-36 doi: 10.1038/nature10600
6. Xu M, Palmer AK, Ding H, Weivoda MM, Pirtskhalava T, White TA, Sepe A, Johnson KO, Stout MB, Giorgadze N, Jensen MD, LeBrasseur NK, Tchkonia T, Kirkland JL. Targeting senescent cells enhances adipogenesis and metabolic function in old age. eLife. 2015; 4:e12997. doi: 10.7554/eLife.12997
7. Roos CM, Zhang B, Palmer AK, Ogrodnik MB, Pirtskhalava T, Thalji NM, Hagler M, Jurk D, Smith LA, Casaclang-Verzosa G, Zhu Y, Schafer MJ, Tchkonia T, et al. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell. 2016; 15:973-77. doi: 10.1111/acel.12458
8. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Hubbard GB, Lenburg M, O'Hara SP, LaRusso NF, Miller JD, et al. The Achilles' heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015; 14:644-58. doi: 10.1111/acel.12344
9. Kirkland JL, Tchkonia T. Clinical strategies and animal models for developing senolytic agents. Exp Gerontol. 2014; 68:19-25. doi: 10.1016/j.exger.2014.10.012
10. Wang E. Senescent human fibroblasts resist programmed cell death, and failure to suppress bcl2 is involved. Cancer Res. 1995; 55:2284-92
11. Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, Dai HM, Ling YY, Stout MB, Pirtskhalava T, Giorgadze N, Johnson KO, Giles CB, Wren JD, Niedernhofer LJ, Robbins PD, et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of antiapoptotic factors. Aging Cell. 2016; 15:428-35. doi: 10.1111/acel.12445
12. Chang J, Wang Y, Shao L, Laberge RM, Demaria M, Campisi J, Janakiraman K, Sharpless NE, Ding S, Feng W, Luo Y, Wang X, Aykin-Burns N, et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat Med. 2016; 22:78-83. doi: 10.1038/nm.4010
13. Yosef R, Pilpel N, Tokarsky-Amiel R, Biran A, Ovadya Y, Cohen S, Vadai E, Dassa L, Shahar E, Condiotti R, Ben-Porath I, Krizhanovsky V. Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL. Nat Commun. 2016; 7:11190. doi: 10.1038/ncomms11190
14. Leverson JD, Phillips DC, Mitten MJ, Boghaert ER, Diaz D, Tahir SK, Belmont LD, Nimmer P, Xiao Y, Ma XM, Lowes KN, Kovar P, Chen J, et al. Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy. Sci Transl Med. 2015; 7:279ra40. doi: 10.1126/scitranslmed.aaa4642
15. Wang Y, Chang J, Liu X, Zhang X, Zhang S, Zhang X, Zhou D, Zheng G. Discovery of piperlongumine as a potential novel lead for the development of senolytic agents. Aging (Albany NY). 2016; 8:2915-26. doi: 10.18632/aging.101100
16. Khan N, Syed DN, Ahmad N, Mukhtar H. Fisetin: a dietary antioxidant for health promotion. Antioxid Redox Signal. 2013; 19:151-62. doi: 10.1089/ars.2012.4901
17. Kimira M, Arai Y, Shimoi K, Watanabe S. Japanese intake of flavonoids and isoflavonoids from foods. J Epidemiol. 1998; 8:168-75. doi: 10.2188/jea.8.168
18. Ishige K, Schubert D, Sagara Y. Flavonoids protect neuronal cells from oxidative stress by three distinct mechanisms. Free Radic Biol Med. 2001; 30:433-46. doi: 10.1016/S0891-5849(00)00498-6
19. Prasath GS, Pillai SI, Subramanian SP. Fisetin improves glucose homeostasis through the inhibition of gluconeogenic enzymes in hepatic tissues of streptozotocin induced diabetic rats. Eur J Pharmacol. 2014; 740:248-54. doi: 10.1016/j.ejphar.2014.06.06520.
20. Prasath GS, Subramanian SP. Antihyperlipidemic effect of fisetin, a bioflavonoid of strawberries, studied in streptozotocin-induced diabetic rats. J Biochem Mol Toxicol. 2014; 28:442-49. doi: 10.1002/jbt.21583
21. Zheng LT, Ock J, Kwon BM, Suk K. Suppressive effects of flavonoid fisetin on lipopolysaccharide-induced microglial activation and neurotoxicity. Int Immunopharmacol. 2008; 8:484-94. doi: 10.1016/j.intimp.2007.12.012
22. Chen YC, Shen SC, Lee WR, Lin HY, Ko CH, Shih CM, Yang LL. Wogonin and fisetin induction of apoptosis through activation of caspase 3 cascade and alternative expression of p21 protein in hepatocellular carcinoma cells SK-HEP-1. Arch Toxicol. 2002; 76:351-59. doi: 10.1007/s00204-002-0346-6
23. Syed DN, Suh Y, Afaq F, Mukhtar H. Dietary agents for chemoprevention of prostate cancer. Cancer Lett. 2008; 265:167-76. doi: 10.1016/j.canlet.2008.02.050
24. Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, Dexter DT. Neuroprotective properties of the natural phenolic antioxidants curcumin and naringenin but not quercetin and fisetin in a 6-OHDA model of Parkinson's disease. Free Radic Res. 2005; 39:1119-25 doi: 10.1080/10715760500233113
25. Yang PM, Tseng HH, Peng CW, Chen WS, Chiu SJ. Dietary flavonoid fisetin targets caspase-3-deficient human breast cancer MCF-7 cells by induction of caspase-7-associated apoptosis and inhibition of autophagy. Int J Oncol. 2012; 40:469-78. doi: 10.3892/ijo.2011.1203
26. Youns M, Abdel Halim Hegazy W. The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways. PLoS One. 2017; 12:e0169335. doi: 10.1371/journal.pone.0169335
27. Kim HJ, Kim SH, Yun JM. Fisetin inhibits hyperglycemia-induced proinflammatory cytokine production by epigenetic mechanisms. Evid Based Complement Alternat Med. 2012; 2012:639469. doi: 10.1155/2012/639469
28. Maher P, Dargusch R, Ehren JL, Okada S, Sharma K, Schubert D. Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes. PLoS One. 2011; 6:e21226. doi: 10.1371/journal.pone.0021226
29. Sahu BD, Kalvala AK, Koneru M, Mahesh Kumar J, Kuncha M, Rachamalla SS, Sistla R. Ameliorative effect of fisetin on cisplatin-induced nephrotoxicity in rats via modulation of NF-κB activation and antioxidant defence. PLoS One. 2014; 9:e105070. doi: 10.1371/journal.pone.0105070
30. Touil YS, Auzeil N, Boulinguez F, Saighi H, Regazzetti A, Scherman D, Chabot GG. Fisetin disposition and metabolism in mice: identification of geraldol as an active metabolite. Biochem Pharmacol. 2011; 82:1731-39. doi: 10.1016/j.bcp.2011.07.097
31. Leverson JD. Chemical parsing: dissecting cell dependencies with a toolkit of selective BCL-2 family inhibitors. Mol Cell Oncol. 2015; 3:e1050155. doi: 10.1080/23723556.2015.1050155
32. Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W, Mitchell JR, Laberge RM, Vijg J, Van Steeg H, Dollé ME, Hoeijmakers JH, de Bruin A, Hara E, Campisi J. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell. 2014; 31:722-33. doi: 10.1016/j.devcel.2014.11.012
33. Currais A, Prior M, Dargusch R, Armando A, Ehren J, Schubert D, Quehenberger O, Maher P. Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice. Aging Cell. 2014; 13:379-90. doi: 10.1111/acel.12185
34. Lucas CM, Milani M, Butterworth M, Carmell N, Scott LJ, Clark RE, Cohen GM, Varadarajan S. High CIP2A levels correlate with an antiapoptotic phenotype that can be overcome by targeting BCL-XL in chronic myeloid leukemia. Leukemia. 2016; 30:1273-81. doi: 10.1038/leu.2016.42
35. Stout MB, Steyn FJ, Jurczak MJ, Camporez JG, Zhu Y, Hawse JR, Jurk D, Palmer AK, Xu M, Pirtskhalava T, Evans GL, de Souza Santos R, Frank AP, et al. 17alphaestradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. J Gerontol A Biol Sci Med Sci. 2017; 72:3-15. doi: 10.1093/gerona/glv309
36. Tchkonia T, Thomou T, Zhu Y, Karagiannides I, Pothoulakis C, Jensen MD, Kirkland JL. Mechanisms and metabolic implications of regional differences among fat depots. Cell Metab. 2013; 17:644-56. doi: 10.1016/j.cmet.2013.03.008
37. Caserta F, Tchkonia T, Civelek VN, Prentki M, Brown NF, McGarry JD, Forse RA, Corkey BE, Hamilton JA, Kirkland JL. Fat depot origin affects fatty acid handling in cultured rat and human preadipocytes. Am J Physiol Endocrinol Metab. 2001; 280:E238-47