Inhibition of tumour cell growth by carnosine: Some possible mechanisms

Amino Acids

Volumn 46, Issue 2, 2014, Pages 327-337

  Hipkiss, Alan R ^a   Gaunitz, Frank ^b  

^a ASTON UNIVERSITY   (United Kingdom)

^b UNIVERSITY HOSPITAL LEIPZIG   (Germany)

Author keywords

Cancer; Carnosine; Glycation; Glycolysis; Metastasis; NAD; Redox biology; Regulation; Signalling; Tumour

Indexed keywords

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; CARNOSINE; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG SCREENING ASSAYS, ANTITUMOR; GLYCOLYSIS; HUMANS; OXIDATION-REDUCTION; SIGNAL TRANSDUCTION;

EID: 84895911229     PISSN: 09394451     EISSN: 14382199     Source Type: Journal    
DOI: 10.1007/s00726-013-1627-5     Document Type: Conference Paper

References (114)

1. Agathocleous M, Love NK, Randlett O, Harris JJ, Liu J, Murray AJ, Harris WA (2012) Metabolic differentiation in the embryonic retina. Nat Cell Biol 14:859-864
2. Alessi DR, Pearce LR, Garcia-Martinez JM (2009) New insights into mTOR signaling: mTORC2 and beyond. Sci Signal 2:pe27
3. Asperger A, Renner C, Menzel M, Gebhardt R, Meixensberger J, Gaunitz F (2011) Identification of factors involved in the anti-tumor activity of carnosine on glioblastomas using a proteomics approach. Cancer Invest 29:272-281
4. Ayyasamy V, Owens KM, Desouki MM, Liang P, Bakin A, Thangaraj K, Buchsbaum DJ, LoBuglio AF, Singh KK (2011) Cellular model of Warburg effect identifies tumor promoting function of UCP2 in breast cancer and its suppression by genipin. PLoS One 6:e24792
5. Baffy G, Derdak Z, Robson SC (2011) Mitochondrial recoupling: a novel therapeutic strategy for cancer? Br J Cancer 105:469-474
6. Baguet A, Everaert I, Achten E, Thomis M, Derave W (2012) The influence of sex, age and heritability on human skeletal muscle carnosine content. Amino Acids 43:13-20
7. Bair WB 3rd, Cabello CM, Uchida K, Bause AS, Wondrak GT (2010) GLO1 overexpression in human malignant melanoma. Melanoma Res 20:85-96
8. Baraniuk JN, El-Amin S, Corey R, Rayhan RU, Timbol C (2013) Carnosine treatment for Gulf War illness: a randomized controlled trial. Glob J Health Sci 5:69-81
9. Bartling B, Hofmann HS, Sohst A, Hatzky Y, Somoza V, Siber RE, Simm A (2011) Prognostic potential and tumor growth-inhibiting effect of plasma advanced glycation end products in non-small cell lung carcinoma. Mol Med 17:980-989
10. Bauer K (2005) Carnosine and homocarnosine, the forgotten, enigmatic peptides of the brain. Neurochem Res 30:1339-1345
11. Bayley JP, Devilee P (2012) The Warburg effect in 2012. Curr Opin Oncol 24:62-67
12. Bensinger SJ, Christofk HR (2012) New aspects of the Warburg effect in cancer cell biology. Semin Cell Dev Biol 23:352-361
13. Bharadwaj LA, Davies GF, Xavier IJ, Ovsenek N (2002) l-Carnosine and verapamil inhibit hypoxia-induced expression of hypoxia inducible factor (HIF-1alpha) in H9c2 cardiomyoblasts. Pharmacol Res 45:175-181
14. Bijnsdorp IV, Capriotti F, Kruyt FA, Losekoot N, Fukushima M, Griffioen AW, Thijssen VL, Peters GJ (2011) Thymidine phosphorylase in cancer cells stimulates human endothelial cell migration and invasion by the secretion of angiogenic factors. Br J Cancer 104:1185-1192
15. Brownson C, Hipkiss AR (2000) Carnosine reacts with a glycated protein. Free Rad Biol Med 28:1564-1570
16. Cano KE, Li YJ, Chen Y (2010) NMR metabolomic profiling reveals new roles of SUMOylation in DNA damage response. Proteome Res 9:5382-5388
17. Cantero AV, Portero-Otin M, Ayala V, Auge N, Sanson M, Elbaz M, Thiers JC, Pamplona R, Salvayre R, Negre-Salvayre A (2007) Methylglyoxal induces advanced glycation end products (AGEs) formation and dysfunction of PDGF receptor-(beta): implications for diabetic atherosclerosis. FASEB J 21:3096-3106
18. Cartwright SP, Bill RM, Hipkiss AR (2012) l-Carnosine affects the growth of Saccharomyces cerevisiae in a metabolism-dependent manner. PLoS One 7:e45006
19. Chengappa KN, Turkin SR, DeSanti S, Bowie CF, Brar JS, Schlicht PJ, Murphy SL, Hetrick ML, Bilder R, Fleet D (2012) A preliminary, randomized, double-blind, placebo-controlled trial of l-carnosine to improve cognition in schizophrenia. Schizophr Res 142:145-152
20. Chez MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C, Komen J (2002) Double-blind, placebo-controlled study of l-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol 17:833-837
21. Chiruta C, Schubert D, Dargusch R, Maher P (2012) Chemical modification of the multitarget neuroprotective compound fisetin. J Med Chem 55:378-389
22. Chuang CH, Hu ML (2008) l-carnosine inhibits metastasis of SK-Hep-1 cells by inhibition of matrix metaoproteinase-9 expression and induction of an antimetastatic gene, nm23-H1. Nutr Cancer 60:526-533
23. Conkright MD, Canettieri G, Screaton R, Guzman E, Miraglia L, Hogenesch JB, Montminy M (2003) TORCs: transducers of regulated CREB activity. Mol Cell 12:413-423
24. Csibi A, Blenis J (2011) Appetite for destruction: the inhibition of glycolysis as a therapy for tuberous sclerosis complex-related tumors. BMC Biol 9:69
25. Cybulski N, Hall MN (2009) TOR complex 2: a signaling pathway of its own. Trends Biochem Sci 34:620-627
26. Engel M, Mazurek S, Eigenbrodt E, Welter C (2004) Phosphoglycerate mutase-derived polypeptide inhibits glycolytic flux and induces cell growth arrest in tumor cell lines. J Biol Chem 279:35803-35812
27. Eto I (2013) Expression of p27Kip 1, a cell cycle repressor protein, is inversely associated with potential carcinogenic risk in the genetic rodent models of obesity and long-lived dwarf mice. Metabolism 62:873-887
28. Frezza C, Gottlieb E (2009) Mitochondria in cancer: not just innocent bystanders. Semin Cancer Biol 19:4-11
29. Gaunitz F, Hipkiss AR (2012) Carnosine and cancer - a perspective. Amino Acids 43:135-142
30. Gimsa U, Kanitz E, Otten W, Aheng C, Tuchscherer M, Ricquier D, Miroux B, Ibrahim SM (2011) Alterations in anxiety-like behaviour following knockout of the uncoupling protein (UCP2) gene in mice. Life Sci 89:677-684
31. Grinio L, Stvolinsky SL (2011) Carnosine and muscle pathologies. In: International congress on carnosine in exercise and disease, Ghent (Abstracts p 46)
32. Grivell AR, Korpelainen EI, Williams CJ, Berry MN (1995) Substrate-dependent utilization of the glycerol 3-phosphate or malate/aspartate redox shuttles by Ehrlich ascites cells. Biochem J 310:665-671
33. Guo G, Gui Y, Gao S, Tang A, Hu X, Huang Y, Jia W, Li Z, He M, Sun L, Song P, Sun X, Zhao X, Yang S, Liang C, Wan S, Zhou F, Chen C, Zhu J, Li X, Jian M, Zhou L, Ye R, Huang P, Chen J, Jiang T, Liu X, Wang Y, Zou J, Jiang Z, Wu R, Wu S, Fan F, Zhang Z, Liu L, Yang R, Liu X, Wu H, Yin W, Zhao X, Liu Y, Peng H, Jiang B, Feng Q, Li C, Xie J, Lu J, Kristiansen K, Li Y, Zhang X, Li S, Wang J, Yang H, Cai Z, Wang J (2012) Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nat Genet 44:17-19
34. Guo J, Ma Q, Zhou X, Shan T, Fan P, Miao D (2013) Inactivation of p27kip1 promotes carcinogens induced liver hepatocarcinogenesis through enhancing inflammatory cytokine secretion and STAT3 signalling activation. J Cell Physiol 228:1967-1976
35. Hamanaka RB, Chandel NS (2012) Targeting glucose metabolism for cancer therapy. J Exp Med 209:211-215
36. Hipkiss AR (2009a) Carnosine and its possible roles in nutrition and health. Adv Food Nutr Res 57:87-154
37. Hipkiss AR (2009b) On the enigma of carnosine's anti-ageing actions. Exp Gerontol 44:237-242
38. Hipkiss AR, Chana H (1998) Carnosine protects proteins against methylgyoxal-mediated modifications. Biochem Biophys Res Commun 248:28-32
39. Hipkiss AR, Michaelis J, Syrris P (1995a) Non-enzymatic glycosylation of the dipeptide l-carnosine, a potential anti-protein-cross-linking agent. FEBS Lett 371:81-85
40. Hipkiss AR, Michaelis J, Syrris P, Dreimanis M (1995b) Strategies for the extension of human life span. Persp Human Biol 1:59-70
41. Holliday R, McFarland GA (1996) Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine. Br J Cancer 73:966-971
42. Horii Y, Shen J, Fujisaki Y, Yoshida K, Nagai K (2012) Effects of l-carnosine on splenic sympathetic nerve activity and tumor proliferation. Neurosci Lett 510:1-5
43. Ikeda T, Kimura K, Hama T, Tamaki N (1980) Activation of rabbit muscle fructose 1,6-bisphosphatatse by histidine and carnosine. J Biochem 87:179-185
44. Ikeda D, Wada S, Yoneda C, Abe H, Watabe S (1999) Carnosine stimulates vimentin expression in cultured rat fibroblasts. Cell Struct Funct 24:79-87
45. Iovine B, Iannella ML, Nocella F, Pricolo MR, Baldi MR, Bevilacqua MA (2011) Carnosine inhibits KRas-mediated HCT-116 proliferation by affecting ATP and ROS production. Cancer Lett 315:122-128
46. Israel M, Schwartz L (2011) The metabolic advantage of tumor cells. Mol Cancer 10:70
47. Jia HJ, Qi XD, Fang SH, Jin YH, Han XY, Wang Y, Wang AM, Zhou HB (2009) Carnosine inhibits high glucose-induced mesangial cell proliferation through mediating cell cycle progression. Regul Pept 154:69-76
48. Jiang X, Kenerson HL, Yeung RS (2011) Glucose deprivation in tuberous sclerosis complex-related tumors. Cell Biosci 1:34
49. Kalaz EB, Evran B, Develi-Is S, Vural P, Dogru-Abbasoglu S, Uysal M (2012) Effect of carnosine on prooxidant-antioxidant balance in several tissues of rats exposed to chromic cold plus immobilization stress. J Pharmacol Sci 120:98-104
50. Koppenol WH, Bounds PL, Dang CV (2011) Otto Warburg's contribution to current concepts of cancer metabolism. Nat Rev Cancer 11:325-337
51. Kusayama M, Wada K, Nagata M, Ishimoto S, Takahashi H, Yoneda M, Nakajima A, Okura M, Kogo M, Kamisaki Y (2011) Critical role of aquaporin 3 on growth of human esophageal and oral squamous cell carcinoma. Cancer Sci 102:1128-1136
52. Liu Z, Ma Y, Yang J, Qin H (2011) Upregulated and downregulated proteins in hepatocellular carcinoma: a systematic review of proteomic profiling studies. OMICS 15:61-71
53. Maher PA, Schubert DR (2009) Metabolic links between diabetes and Alzheimer's disease. Expert Rev Neurother 9:617-630
54. Mai A (2012) Revelations into resveratrol's mechanism. Nat Med 18:501
55. Mair W, Morantte I, Rodrigues AP, Manning G, Montminy M, Shaw RJ, Dillin A (2011) Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470:404-408
56. Mazurek S (2011) Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol 43:969-980
57. McFarland GA, Holliday R (1994) Retardation of the senescence of cultured human diploid fibroblasts by carnosine. Exp Cell Res 212:167-175
58. McFarland GA, Holliday R (1999) Further evidence for the rejuvenating effects of the dipeptide l-carnosine on cultured human diploid fibroblasts. Exp Gerontol 34:35-45
59. Mor I, Cheung EC, Vousden KH (2011) Control of glycolysis through regulation of PFK1: old friends and recent additions. Cold Spring Harb Symp Quant Biol 76:211-206
60. Nagai K, Suda T (1986) Antineoplastic effects of carnosine and beta-alanine-physiological considerations of its antineoplastic effects. Nihon Seirigaku Zasshi 48:741-747
61. Nakajima Y, Madhyastha R, Maruyama M (2009) 2-Deoxy-d-ribose, a downstream mediator of thymidine phosphorylase, regulates tumor angiogenesis and progression. Anticancer Agents Med Chem 9:239-245
62. Oya-Ito T, Naito Y, Takagi T, Handa O, Matsui H, Yamada M, Shima K, Yoshikawa T (2011) Heat-shock protein 27 (Hsp27) as a target of methylglyoxal in gastrointestinal cancer. Biochim Biophys Acta 1812:769-781
63. Panzanelli P, Cantino D, Sassòe-Pognetto M (1997) Co-localization of carnosine and glutamate in photoreceptors and bipolar cells of the frog retina. Brain Res 758:143-152
64. Pognetto MS, Panzanelli P, Fasolo A, Cantino D (1992) Expression of carnosine-like immunoreactivity during retinal development in the clawed frog (Xenopus laevis). Brain Res Dev Brain Res 70:134-138
65. Pópulo H, Lopes JM, Soares P (2012) The mTOR signalling pathway in human cancer. Int J Mol Sci 13:1886-1918
66. Porporato PE, Dhup S, Dadhich RK, Copetti T, Sonveaux P (2011) Anticancer targets in the glycolytic metabolism of tumors: a comprehensive review. Front Pharmacol 2:49
67. Quinn PJ, Boldyrev AA, Formazuyk VE (1992) Carnosine - its properties, functions and potential therapeutic applications. Mol Aspects Med 13:379-444
68. Rabbani N, Thornalley PJ (2008) The dicarbonyl proteome: proteins susceptible to dicarbonyl glycation at functional sites in health, aging and disease. Ann N Y Acad Sci 1126:124-127
69. Renner C, Seyffarth A, de Arriba S, Meixensberger J, Gebhardt R, Gaunitz F (2008) Carnosine inhibits growth of cells isolated from human glioblastoma multiforme. Int J Pept Res Ther 14:127-135
70. Renner C, Asperger A, Seyffarth A, Meixensberger J, Gebhardt R, Gaunitz F (2010a) Carnosine inhibits ATP production in cells from malignant glioma. Neurol Res 32:101-105
71. Renner C, Zemitzsch N, Fuchs B, Geiger KD, Hermes M, Hengstler J, Gebhardt R, Meixensberger J, Gaunitz F (2010b) Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model. Mol Cancer 9:2
72. Robbins D, Zhao Y (2011) New aspects of mitochondrial uncoupling proteins (UCPs) and their roles in tumorigenesis. Int J Mol Sci 12:5285-5293
73. Rodríguez-Enríquez S, Gallardo-Pérez JC, Marín-Hernández A, Moreno-Sánchez R (2012) The Warburg hypothesis and the ATP supply in cancer cells. Is oxidative phosphorylation impaired in malignant neoplasias? Curr Pharm Biotechnol (In press)
74. Rousset S, Mozo J, Dujardin G, Emre Y, Masscheleyn S, Ricquier D, Cassard-Doulcier AM (2007) UCP2 is a mitochondrial transporter with an unusual very short half-life. FEBS Lett 581:479-482
75. Rybakova YS, Boldyrev AA (2012) Effect of carnosine and related compounds on proliferation of cultured rat pheochromocytoma PC-12 cells. Bull Exp Biol Med 154:136-140
76. Rybakova J, Akkuratov E, Kulebyakin K, Brodskaya O, Dizhevskaya E, Boldyrev A (2012) Receptor-mediated oxidative stress in murine cerebellar neurons is accompanied by phosphorylation of Map (ERK1/2) kinase. Curr Aging Sci 5:225-230
77. Sakai M, Matsumoto M, Tujimura T, Yongheng C, Noguchi T, Inagaki K, Inoue H, Hosooka T, Takazawa K, Kido Y, Yasuda K, Hiramatsu R, Matsuki Y, Kasuga M (2012) CITED2 links hormonal signalling to PGC-1α acetylation in the regulation of gluconeogenesis. Nat Med 41:612-617
78. Salminen A, Kaarniranta K (2012) AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev 11:230-241
79. Santel T, Pflug G, Hemdan NY, Schäfer A, Hollenbach M, Buchold M, Hintersdorf A, Lindner I, Otto A, Bigl M, Oerlecke I, Hutschenreuther A, Sack U, Huse K, Groth M, Birkemeyer C, Schellenberger W, Gebhardt R, Platzer M, Weiss T, Vijayalakshmi MA, Krüger M, Birkenmeier G (2008) Curcumin inhibits glyoxalase 1: a possible link to its anti-inflammatory and anti-tumor activity. PLoS One 3:e3508
80. Scalia M, Satriano C, Greca R, Stella AM, Rizzarelli E, Spina-Purrello V (2013) PARP-1 inhibitors DPQ and PJ-34 negatively modulate proinflammatory commitment of human glioblastoma cells. Neurochem Res 38:50-58
81. Seyfried TN, Kiebish MA, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P (2011) Metabolic management of brain cancer. Biochim Biophys Acta 1807:577-594
82. Seyfried TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P (2012) Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Res 100:310-326
83. Shao R, Zhang FP, Tian F, Anders Friberg P, Wang X, Sjöland H, Billig H (2004) Increase of SUMO-1 expression in response to hypoxia: direct interaction with HIF-1alpha in adult mouse brain and heart in vivo. FEBS Lett 569:293-300
84. Shen L, Zhu Z, Huang Y, Shu Y, Sun M, Xu H, Zhang G, Guo R, Wei W, Wu W (2010) Expression profile of multiple aquaporins in human gastric carcinoma and clinical significance. Biomed Pharmacother 64:313-318
85. Son DO, Satsu H, Kiso Y, Totsuka M, Shimizu M (2008) Inhibitory effect of carnosine on interleukin-8 production in intestinal epithelial cells through translational regulation. Cytokine 42:265-276
86. Spina-Purrello V, Gilberto S, Barresi V, Nicoletti VG, Giuffrida Stella AM, Rizzarelli E (2010) Modulation of PARP-1 and PARP-2 expression by l-carnosine and trehalose after LPS and INF-gamma-induced oxidative stress. Neurochem Res 35:2144-2153
87. Spoden GA, Rostek U, Lechner S, Mitterberger M, Mazurek S, Zwerschke W (2009) Pyruvate kinase isoenzyme M2 is a glycolytic sensor differentially regulating cell proliferation, cell size and apoptotic cell death dependent on glucose supply. Exp Cell Res 315:2765-2774
88. Stuerenberg HJ, Kunze K (1999) Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle and rat muscles. Arch Gerontol Geriatr 29:107-113
89. Szwergold BS (2005) Intrinsic toxicity of glucose, due to non-enzymatic glycation, is controlled in vivo by deglycation systems including: FN3K-mediated deglycation of fructosamines and transglycation of aldosamines. Med Hypotheses 65:337-348
90. Tallon MJ, Harris RC, Maffulli N, Tarnopolsky MA (2007) Carnosine, taurine and enzyme activities of human skeletal muscle fibres from elderly subjects with osteoarthritis and young moderately active subjects. Biogerontol 8:129-137
91. Talukdar D, Ray S, Ray M, Das S (2008) A brief critical overview of the biological effects of methylglyoxal and further evaluation of a methylglyoxal-based anticancer formulation in treating cancer patients. Drug metabol Drug Interact 23:175-210
92. Thornalley PJ, Rabbani N (2011) Glyoxalase in tumourigenesis and multidrug resistance. Semin Cell Dev Biol 22:318-325
93. Tomonaga S, Yamane H, Onitsuka E, Yamada S, Sato M, Takahata Y, Morimatsu F, Furuse M (2008) Carnosine-induced antidepressant-like activity in rats. Pharmacol Biochem Behav 89:627-632
94. Tsoi B, He RR, Yang DH, Li YF, Li XD, Li WX, Abe K, Kurihara H (2011) Carnosine ameliorates stress-induced glucose metabolism disorder in restrained mice. J Pharmacol Sci 117:223-239
95. Turk Z (2010) Glycotoxins, carbonyl stress and relevance to diabetes and its complications. Physiol Res 59:147-156
96. Vander Heiden MG (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324:1029-1033
97. Vander Heiden MG (2011) Targeting cancer metabolism: a therapeutic window opens. Nat Rev Drug Discov 10:671-684
98. Vander Heiden MG, Locasale JW, Swanson KD, Sharfi H, Heffron GJ, Amador-Noguez D, Christofk HR, Wagner G, Rabinowitz JD, Asara JM, Cantley LC (2010) Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science 329:1492-1499
99. Verkman AS (2005) More than just water channels: unexpected cellular roles of aquaporins. J Cell Sci 118:3225-3232
100. Verkman AS, Hara-Chikuma M, Papadopoulos MC (2008) Aquaporins-new players in cancer biology. J Mol Med (Berl) 86:523-529
101. Villa-Cuesta E, Boylan JM, Tatar M, Gruppuso PA (2011) Resveratrol inhibits protein translation in hepatic cells. PLoS One 6:e29513
102. Wang Y, Li G, Goode J, Paz JC, Ouyang K, Screaton R, Fischer WH, Chen J, Tabas I, Montminy M (2012) Inositol-1,4,5-triphosphate receptor regulates hepatic gluconeogenesis in fasting and diabetes. Nature 485:128-132
103. Wang J-P, Yang Z-T, Liu C, He Y-H, Zhao S-S (2013) l-Carnosine inhibits cell apoptosis through signal transducer and activator transcription 3 signalling pathway after acute focal cerebral ischemia. Brain Res 1507:125-133
104. Warburg O (1956) On the origin of cancer cells. Science 123:309-314
105. Wilson WR, Hay MP (2011) Targeting hypoxia in cancer therapy. Nat Rev Cancer 11:383-410
106. Wondrak GT, Jacobson MK, Jacobson EL (2006) Antimelanoma activity of apoptogeneic carbonyl scavengers. J Pharmacol Exp Ther 316:805-814
107. Xia Y, Choi HK, Lee K (2012) Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. Eur J Med Chem 49:24-40
108. Xie J, Ponuwei GA, Moore CE, Willars GB, Tee AR, Herbert TP (2011) cAMP inhibits mammalian target of rapamycin complex-1 and -2 (mTORC1 and 2) by promoting complex dissociation and inhibiting kinase activity. Cell Sig 23:1927-1935
109. Xu H, Xu Y, Zhang W, Shen L, Yang L, Xu Z (2011) Aquaporin-3 positively regulates matrix metalloproteinases via PI3K/AKT signal pathway in human gastric carcinoma SGC7901 cells. J Exp Clin Cancer Res 30:86
110. Yang JH, Yan CX, Chen XJ, Zhu YS (2011) Expression of aquaglyceroporins in epithelial ovarian tumours and their clinical significance. J Int Med Res 39:702-711
111. Yellen P, Saqcena M, Salloum D, Feng J, Preda A, Xu L, Rodrik-Outmezguine V, Foster DA (2011) High-dose rapamycin induces apoptosis in human cancer cells by dissociating mTOR complex 1 and suppressing phosphorylation of 4E-BP1. Cell Cycle 10:3948-3956
112. Yuan M, Luo M, Song Y, Xu Q, Wang X, Cao Y, Bu X, Ren Y, Hu X (2011) Identification of curcumin derivatives as human glyoxalase I inhibitors: a combination of biological evaluation, molecular docking, 3D-QSAR and molecular dynamics simulation studies. Bioorg Med Chem 19:1189-1196
113. Zhang JH, Lu Q, Shi WJ, Wu ZZ, Wang LS (2005) The induction apoptosis of HL-60 cells by low molecular weight compounds of taurine, ornithine and carnosine from new born calf liver. Zhongguo Ying Yong Sheng Li Xue Za Zhi 21:200-205
114. Zhang Y, Okamura S, Kudo T, Masuo T, Mori M (2011) Calcineurin inhibition by polaprezinc in rats with experimentally-induced colitis. Life Sci 88:432-439