Rottlerin and curcumin: A comparative analysis

Annals of the New York Academy of Sciences

Volumn 1259, Issue 1, 2012, Pages 65-76

  Maioli, Emanuela ^a   Torricelli, Claudia ^a   Valacchi, Giuseppe ^b,c  

^a UNIVERSITY OF SIENA   (Italy)

^b UNIVERSITY OF FERRARA   (Italy)

^c Kyung Hee University   (South Korea)

Author keywords

Anti inflammatory; Antiamyloid; Antioxidant; Curcumin; Rottlerin

Indexed keywords

1,1 DIPHENYL 2 PICRYLHYDRAZYL; ACETYLCYSTEINE; ALPHA SYNUCLEIN; AMYLOID BETA PROTEIN; ARACHIDONATE 15 LIPOXYGENASE; BETA LACTAMASE; CASPASE 3; CURCUMIN; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; DNA; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3A; HEME OXYGENASE 1; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN KINASE C GAMMA; ROTTLERIN; SMALL INTERFERING RNA; STAT PROTEIN; TRANSCRIPTION FACTOR NRF2;

ALZHEIMER DISEASE; AMYLOIDOSIS; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; ARTICLE; CANCER CELL; CELL CULTURE; CELL STRAIN MCF 7; COMPARATIVE STUDY; DNA SEQUENCE; DOWN REGULATION; DRUG BIOAVAILABILITY; DRUG SOLUBILITY; DRUG STRUCTURE; ENDOTHELIUM CELL; EPIGENETICS; HEPATOMA CELL; HUMAN; IC 50; IN VITRO STUDY; IN VIVO STUDY; LEUKEMIA CELL; MALLOTUS PHILIPPINENSIS; PARKINSON DISEASE; PROTEIN BLOOD LEVEL; PROTEIN DENATURATION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; UPREGULATION; UTERINE CERVIX CANCER;

EID: 84863516716     PISSN: 00778923     EISSN: 17496632     Source Type: Book Series    
DOI: 10.1111/j.1749-6632.2012.06514.x     Document Type: Article

References (94)

1. Maheshwari, R.K. et al 2006. Multiple biological activities of curcumin: a short review. J. Life Sci. 78: 2081-2087.
2. Gschwendt, M. et al 1994. Rottlerin, a novel protein kinase inhibitor. Biochem. Biophys. Res. Commun. 199: 63-98.
3. Bain, J. et al 2007. The selectivity of protein kinase inhibitors: a further update. Biochem. J. 408: 297-315.
4. Soltoff, S.P. 2001. Rottlerin is a mitochondrial uncoupler that decreases cellular ATP levels and indirectly blocks protein kinase Cdelta tyrosine phosphorylation. J. Biol. Chem. 276: 37986-37992.
5. Tillman, D.M. et al 2003. Rottlerin sensitizes colon carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via uncoupling of the mitochondria independent of protein kinase C. Cancer Res. 63: 5118-5125.
6. Xu, S.Z. 2007. Rottlerin induces calcium influx and protein degradation in cultured lenses independent of effects on protein kinase C delta. Basic Clin. Pharmacol. Toxicol. 101: 459-464.
7. Tapia, J.A., R.T. Jensen & L.J. García-Marín 2006. Rottlerin inhibits stimulated enzymatic secretion and several intracellular signaling transduction pathways in pancreatic acinar cells by a non-PKC-delta-dependent mechanism. Biochim. Biophys. Acta 1763: 25-38.
8. Reddy, S. & B.B. Aggarwal 1994. Curcumin is a non-competitive and selective inhibitor of phosphorylase kinase. FEBS Lett. 341: 19-22.
9. Kuttan, R. et al 1985. Potential anticancer activity of turmeric (Curcuma longa). Cancer Lett. 29: 197-202.
10. Davies, S.P. et al 2000. Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351: 95-105.
11. Soltoff, S.P. 2007. Rottlerin: an inappropriate and ineffective inhibitor of PKCdelta. Trends Pharmacol. Sci. 28: 453-458.
12. Maioli, E., C. Torricelli & G. Valacchi 2011. Rottlerin and cancer: novel evidences and mechanisms. Scientific World Journal. doi:
13. Liu, J.Y., S.J. Lin & J.K. Lin 1993. Inhibitory effects of curcumin on protein kinase C activity induced by 12-O-tetradecanoyl-phorbol-13-acetate in NIH 3T3 cells. Carcinogenesis 14: 857-861.
14. Hasmeda, M. & G.M. Polya 1996. Inhibition of cyclic AMP-dependent protein kinase by curcumin. Phytochemistry 42: 599-605.
15. Conboy, L. et al 2009. Curcumin-induced degradation of PKC delta is associated with enhanced dentate NCAM PSA expression and spatial learning in adult and aged Wistar rats. Biochem. Pharmacol. 77: 1254-1265.
16. Kao, H.H. et al 2011. Kinase gene expression and subcellular protein expression pattern of protein kinase C isoforms in curcumin-treated human hepatocellular carcinoma Hep 3B cells. Plant Foods Hum. Nutr. 66: 136-142.
17. Majhi, A. et al 2010. Binding of curcumin and its long chain derivatives to the activator binding domain of novel protein kinase C. Bioorg. Med. Chem. 18: 1591-1598.
18. Das, J. et al 2011. Binding of isoxazole and pyrazole derivatives of curcumin with the activator binding domain of novel protein kinase C. Bioorg. Med. Chem. 19: 6196-6202.
19. Arfan, M. et al 2007. Antioxidant activity of extracts of Mallotus philippinensis fruit and bark. J. Food Lipids 14: 280-297.
20. Longpre, J.M. & G. Loo 2008. Protection of human colon epithelial cells against deoxycholate by rottlerin. Apoptosis 13: 1162-1171.
21. Maioli, E. et al 2009. Rottlerin inhibits ROS formation and prevents NFkappaB activation in MCF-7 and HT-29 cells. J. Biomed. Biotechnol. [Epub ahead of print]
22. Priyadarsini, K.I. et al 2003. Role of phenolic O-H and methylene hydrogen on the free radical reactions and antioxidant activity of curcumin. Free Radic. Biol. Med. 35: 475-484.
23. Feng, J.Y. & Z.Q. Liu 2009. Phenolic and enolic hydroxyl groups in curcumin: which plays the major role in scavenging radicals? J. Agric. Food Chem. 57: 11041-11046.
24. Ahsan, H. et al 1999. Pro-oxidant, anti-oxidant and cleavage activities on DNA of curcumin and its derivatives demethoxycurcumin and bisdemethoxycurcumin. Chem. Biol. Interact. 121: 161-175.
25. Yoshino, M. et al 2004. Prooxidant activity of curcumin: copper-dependent formation of 8-hydroxy-2'-deoxyguanosine in DNA and induction of apoptotic cell death. Toxicol. In vitro 18: 783-789.
26. Park, E.J. et al 2010. Rottlerin induces heme oxygenase-1 (HO-1) up-regulation through reactive oxygen species (ROS) dependent and PKC d-independent pathway in human colon cancer HT29 cells. Biochimie 92: 110-115.
27. Zhang, H. & H.J. Forman 2008. Acrolein induces heme oxygenase-1 through PKC-delta and PI3K in human bronchial epithelial cells. Am. J. Respir. Cell. Mol. Biol. 38: 483-490.
28. Shih, R.H. et al 2011. Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells. J Neuroinflammation 8: 104.
29. Kim, K.M. et al 2010. Puerarin suppresses AGEs-induced inflammation in mouse mesangial cells: a possible pathway through the induction of heme oxygenase-1 expression. Toxicol. Appl. Pharmacol. 244: 106-113.
30. Sikorski, E.M. et al 2004. The story so far: Molecular regulation of the heme oxygenase-1 gene in renal injury. Am. J. Physiol. Renal Physiol. 286: 425-441.
31. Motterlini, R. et al 2000. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic. Biol. Med. 28: 1303-1312.
32. McNally, S.J. et al 2007. Curcumin induces heme oxygenase 1 through generation of reactive oxygen species. Int. J. Mol. Med. 19: 165-172.
33. Pae, H.O. et al 2007. Roles of heme oxygenase-1 in curcumin-induced growth inhibition in rat smooth muscle cells. Exp. Mol. Med. 39: 267-277.
34. Rushworth, S.A. et al 2006. Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochem. Biophys. Res. Commun. 341: 1007-1016.
35. Herman, J.G. & S.B. Baylin 2003. Gene silencing in cancer in association with promoter hypermethylation. N. Engl. J. Med. 349: 2042-2054.
36. Khor, T.O. et al 2011. Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation. Biochem. Pharmacol. 82: 1073-1078.
37. Shu, L. et al 2011. Epigenetic CpG demethylation of the promoter and reactivation of the expression of neurog1 by curcumin in prostate LNCaP cells. AAPS J. 13: 606-614. doi:.
38. Jha, A.K. et al 2010. Reversal of hypermethylation and reactivation of the RARβ2 gene by natural compounds in cervical cancer cell lines. Folia Biol. (Praha). 56: 195-200.
39. Liu, Y.L. et al 2011. Hypomethylation effects of curcumin, demethoxycurcumin and bisdemethoxycurcumin on WIF-1 promoter in non-small cell lung cancer cell lines. Mol. Med. Report. 4: 675-679.
40. Liu, Z. et al 2009. Curcumin is a potent DNA hypomethylation agent. Bioorg. Med. Chem. Lett. 19: 706-709.
41. Medina-Franco, J.L. et al 2011. Natural products as DNA methyltransferase inhibitors: a computer-aided discovery approach. Mol. Divers. 15: 293-304.
42. Chen, Z.F. et al 2006. The effect of PKC-delta inhibitor Rottlerin on human colon cancer cell line SW1116 and its mechanism. Zhonghua Zhong Liu Za Zhi. 28: 564-567.
43. Lu, R. et al 2007. Inhibition of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway decreases DNA methylation in colon cancer cells. J. Biol. Chem. 282: 12249-12259.
44. McGovern, S.L. & B.K. Shoichet 2003. Kinase inhibitors: not just for Kinases anymore. J. Med. Chem. 46: 1478-1483.
45. Coan, K.E. et al 2009. Promiscuous aggregate-based inhibitors promote enzyme unfolding. J. Med. Chem. 52: 2067-2075.
46. Lim, J.H. et al 2008. Rottlerin induces pro-apoptotic endoplasmic reticulum stress through the protein kinase C-delta-independent pathway in human colon cancer cells. Apoptosis 13: 1378-1385.
47. Lai, E., T. Teodoro & A. Volchuk 2007. Endoplasmic reticulum stress: signaling the unfolded protein response. Physiology (Bethesda) 22: 193-201.
48. Wu, S.H. et al 2010. Curcumin induces apoptosis in human non-small cell lung cancer NCI-H460 cells through ER stress and caspase cascade- and mitochondria-dependent pathways. Anticancer Res. 30: 2125-2133.
49. Wahlang, B., Y.B. Pawar & A.K. Bansal 2011. Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model. Eur. J. Pharm. Biopharm. 77: 275-282.
50. Doak, A.K. et al Colloid formation by drugs in simulated intestinal fluid. J. Med. Chem. 53: 4259-4265.
51. Feng, B.Y. et al 2008. Small-molecule aggregates inhibit amyloid polymerization. Nat. Chem. Biol. 4: 197-199.
52. Sarkar, N., M. Kumar & V.K. Dubey 2011. Exploring possibility of promiscuity of amyloid inhibitor: studies on effect of selected compounds on folding and amyloid formation of proteins. Process Biochem. 46: 1179-1185.
53. Sarkar, N., M. Kumar & V.K. Dubey 2011. Rottlerin dissolves pre-formed protein amyloid: a study on hen egg white lysozyme. Biochim. Biophys. Acta. 1810: 809-814.
54. McGovern, S.L. et al 2002. A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J. Med. Chem. 45: 1712-1722.
55. Reinke, A.A. & J.E. Gestwicki 2007. Structure-activity relationships of amyloid Beta-aggregation inhibitors based on curcumin: influence of linker length and flexibility. Chem. Biol. Drug Des. 70: 206-215.
56. Subash, C. et al 2011. Multitargeting by curcumin as revealed by molecular interaction studies. Nat. Prod. Rep. 28: 1937-1955. doi:.
57. Pandey, N. et al 2008. Curcumin inhibits aggregation of alpha-synuclein. Acta Neuropathol. 115: 479-489.
58. Ono, K. et al 2004. Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J. Neurosci. Res. 75: 742-750.
59. Kim, H. et al 2005. Effects of naturally occurring compounds on fibril formation and oxidative stress of beta-amyloid. J. Agric. Food Chem. 53: 8537-8541.
60. Kim, D.S., S.Y. Park & J.K. Kim 2001. Curcuminoids from curcuma longa L. (zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from abeta(1-42) insult. Neurosci. Lett. 303: 57-61.
61. Re, F. et al 2010. Beta amyloid aggregation Inhibitors: small molecules as candidate drugs for therapy of Alzheimer's disease. Curr. Med. Chem. 17: 2990-3006.
62. Yang, F. et al 2005. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J. Biol. Chem. 280: 5892-5901.
63. Mourtas, S. et al 2011. Curcumin-decorated nanoliposomes with very high affinity for amyloid-β1-42 peptide. Biomaterials. 32: 1635-1645.
64. Daval, M. et al 2010. The effect of curcumin on human islet amyloid polypeptide misfolding and toxicity. Amyloid 17: 118-128.
65. Hafner-Bratkovic, I. et al 2008. Curcumin binds to the alpha-helical intermediate and to the amyloid form of prion protein-a new mechanism for the inhibition of PrP(Sc) accumulation. J. Neurochem. 104: 1553-1564.
66. Steven, S.S. et al 2009. Effect of curcumin on the amyloid fibrillogenesis of hen egg-white lysozyme. Biophys. Chem. 144: 78-87.
67. Ishii, R. et al 2002. Inhibitory effects of phloroglucinol derivatives from Mallotus japonicus on nitric oxide production by a murine macrophage-like cell line, RAW 264.7, activated by lipopolysaccharide and interferon-gamma. Biochim. Biophys. Acta. 15: 74-82.
68. Ishii, R. et al 2002. Prostaglandin E(2) production and induction of prostaglandin endoperoxide synthase-2 is inhibited in a murine macrophage-like cell line, RAW 264.7, by Mallotus japonicus phloroglucinol derivatives. Biochim. Biophys. Acta. 1571: 115-123.
69. Park, Y.S. et al 2007. Acrolein induces Cyclooxygenase-2 and prostaglandin production in human umbilical vein endothelial cells: roles of p38 MAP Kinase. Arterioscler. Thromb. Vasc. Biol. 27: 1319-1325.
70. Hsieh, H.L. et al 2007. BK-induced COX-2 expression via PKC-δ-dependent activation of p42/p44 MAPK and NF-κB in astrocytes. Cell. Signal. 19: 330-340.
71. Jang, B.C. 2009. Induction of COX-2 in human airway cells by manganese: role of PI3K/PKB, p38 MAPK, PKCs, Src, and glutathione depletion. Toxicol. In vitro 23: 120-126.
72. Kwak, H.J. et al 2010. The cardioprotective effects of zileuton, a 5-lipoxygenase inhibitor, are mediated by COX-2 via activation of PKCδ. Cell. Signal. 22: 80-87.
73. Hsieh, H.L. et al 2008. PKC-δ/c-Src-mediated EGF receptor transactivation regulates thrombin-induced COX-2 expression and PGE2 production in rat vascular smooth muscle cells. Biochim. Biophys. Acta 1783: 1563-1575.
74. Torricelli, C. et al 2008. Rottlerin inhibits the nuclear factor kappaB/cyclin-D1 cascade in MCF-7 breast cancer cells. Life Sci. 82: 638-643.
75. Valacchi, G. et al 2009. Rottlerin: a multifaced regulator of keratinocyte cell cycle. Exp. Dermatol. 18: 516-521.
76. Valacchi, G. et al 2011. Rottlerin exhibits antiangiogenic effects in vitro. Chem. Biol. Drug Des. 77: 460-470.
77. Park, E.J. & T.K. Kwon 2011. Rottlerin enhances IL-1b-induced COX-2 expression through sustained p38 MAPK activation in MDA-MB-231 human breast cancer cells. Exp. Mol. Med. 4: 669-675.
78. Shanmugam, M. et al 2001. A role for protein kinase C delta in the differential sensitivity of MCF-7 and MDA-MB 231 human breast cancer cells to phorbol ester-induced growth arrest and p21(WAFI/CIP1) induction. Cancer Lett. 172: 43-53.
79. Xu, B. et al 2004. Role of Protein Kinase C isoforms in the regulation of Interleukin-13-induced 15-Lipoxygenase gene expression in human monocytes. J. Biol. Chem. 279: 15954-15960.
80. Bhattacharjee, A. et al 2006. Monocyte 15-Lipoxygenase expression is regulated by a novel cytosolic signaling complex with Protein Kinase C d and tyrosine-phosphorylated Stat3. J. Immunol. 177: 3771-3781.
81. Singh, S. & B.B. Aggarwal 1995. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J. Biol. Chem. 270: 24995-25000.
82. Rao, C.V. 2007. Regulation of COX and LOX by curcumin. Adv. Exp. Med. Biol. 595: 213-226.
83. Menon, V.P. & A.R. Sudheer 2007. Antioxidant and anti-inflammatory properties of curcumin. Adv. Exp. Med. Biol. 595: 105-125.
84. Zhang, F. et al 1999. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signaling complex. Carcinogenesis 20: 445-451.
85. Zhang, F. et al 1999. Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. Carcinogenesis. 20: 445-451.
86. Ireson, C. et al 2001. Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E2 production. Cancer Res. 61: 1058-1064.
87. Lin, J.K. 2004. Suppression of protein kinase C and nuclear oncogene expression as possible action mechanisms of cancer chemoprevention by Curcumin. Arch. Pharm. Res. 27: 683-692.
88. Kim H.Y. et al 2003. Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine phosphatase 2 in brain microglia. J. Immunol. 171: 6072-6079.
89. Lim, H.W., H.Y. Lim & K.P. Wong 2009. Uncoupling of oxidative phosphorylation by curcumin: implication of its cellular mechanism of action. Biochem. Biophys. Res. Commun. 389: 187-192.
90. Zaidi, S.F.H. et al 2009. Potent bactericidal constituents from Mallotus philippinensis against clarithromycin and metronidazole resistant strains of Japanese and Pakistani Helicobacter pylori. Biol. Pharm. Bull. 32: 631-636.
91. De, R. et al 2009. Antimicrobial activity of curcumin against Indian Helicobacter pylori and also during mice infection. Antimicrob. Agents Chemother. 53: 1592-1597.
92. Balgi, A.D. et al 2009. Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling. PLoS One 4: e7124.
93. Yu, S. et al 2008. Curcumin inhibits Akt/mammalian target of rapamycin signaling through protein phosphatase dependent mechanism. Mol. Cancer Ther. 7: 2609-2620.
94. Zhang, D. et al 2007. Neuroprotective effect of protein kinase Cdelta inhibitor rottlerin in cell culture and animal models of Parkinson's disease. J. Pharmacol. Exp. Ther. 322: 913-922.