N-Butylidenephthalide protects against dopaminergic neuron degeneration and α-synuclein accumulation in Caenorhabditis elegans models of Parkinson's disease

PLoS ONE

Volumn 9, Issue 1, 2014, Pages

  Fu, Ru Huei ^a,b   Harn, Horng Jyh ^b   Liu, Shih Ping ^a,b   Chen, Chang Shi ^c   Chang, Wen Lin ^a   Chen, Yue Mi ^a   Huang, Jing En ^a   Li, Rong Jhu ^a   Tsai, Sung Yu ^a   Hung, Huey Shan ^a,b   Shyu, Woei Cherng ^a,b   Lin, Shinn Zong ^a,b,d,e   Wang, Yu Chi ^f  

^a CHINA MEDICAL UNIVERSITY   (Taiwan)

^b CHINA MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^c NATIONAL CHENG KUNG UNIVERSITY   (Taiwan)

^d CHINA MEDICAL UNIVERSITY BEIGANG HOSPITAL   (Taiwan)

^e Tainan Municipal An Nan Hospital China Medical University   (Taiwan)

^f INDUSTRIAL TECHNOLOGY RESEARCH INSTITUTE   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; DOPAMINE; GREEN FLUORESCENT PROTEIN; LIPID; N BUTYLIDENEPHTHALIDE; OXIDOPAMINE; PLANT MEDICINAL PRODUCT; PROTEASOME; UNCLASSIFIED DRUG;

ANGELICA SINENSIS; ANIMAL CELL; ANTIPARKINSONIAN ACTIVITY; APOPTOSIS; ARTICLE; CAENORHABDITIS ELEGANS; CONTROLLED STUDY; DOPAMINERGIC NERVE CELL; DRUG ACTIVITY; DRUG EFFICACY; DRUG STRUCTURE; EGL 1 GENE; ENZYME ACTIVITY; FAT CONTENT; FEEDING BEHAVIOR; GENE; GENE EXPRESSION; LIFE EXTENSION; MUSCLE CELL; NERVE CELL DEGENERATION; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PROTEIN AGGREGATION; PROTEIN EXPRESSION; RPN 6 GENE; SIGNAL TRANSDUCTION; TRANSGENIC ORGANISM;

ALPHA-SYNUCLEIN; ANGELICA SINENSIS; ANIMALS; ANTIPARKINSON AGENTS; CAENORHABDITIS ELEGANS; CAENORHABDITIS ELEGANS PROTEINS; DISEASE MODELS, ANIMAL; DOPAMINE; DOPAMINERGIC NEURONS; DRUGS, CHINESE HERBAL; GENE EXPRESSION REGULATION; HUMANS; LONGEVITY; MUSCLE CELLS; OXIDOPAMINE; PARKINSON DISEASE; PHTHALIC ANHYDRIDES; PROTEASOME ENDOPEPTIDASE COMPLEX; REPRESSOR PROTEINS; TRANSGENES;

EID: 84896962462     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0085305     Document Type: Article

References (96)

1. Coelho M, Ferreira JJ (2012) Late-stage Parkinson disease. Nat Rev Neurol 8: 435-442.
2. Hansen C, Li JY (2012) Beyond alpha-synuclein transfer: pathology propagation in Parkinson's disease. Trends Mol Med 18: 248-255.
3. Youle RJ, van der Bliek AM (2012) Mitochondrial fission, fusion, and stress. Science 337: 1062-1065.
4. Blandini F, Armentero MT (2012) Animal models of Parkinson's disease. FEBS J 279: 1156-1166.
5. Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM (2002) Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295: 865-868. (Pubitemid 34118369)
6. Snyder H, Mensah K, Theisler C, Lee J, Matouschek A, et al. (2003) Aggregated and monomeric alpha-synuclein bind to the S6′ proteasomal protein and inhibit proteasomal function. J Biol Chem 278: 11753-11759. (Pubitemid 36800143)
7. Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D (2004) Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 305: 1292-1295. (Pubitemid 39129234)
8. Bussell R Jr, Eliezer D (2004) Effects of Parkinson's disease-linked mutations on the structure of lipid-associated alpha-synuclein. Biochemistry 43: 4810-4818.
9. Jensen PH, Nielsen MS, Jakes R, Dotti CG, Goedert M (1998) Binding of alpha-synuclein to brain vesicles is abolished by familial Parkinson's disease mutation. J Biol Chem 273: 26292-26294. (Pubitemid 28471629)
10. Binukumar BK, Bal A, Kandimalla RJ, Gill KD (2010) Nigrostriatal neuronal death following chronic dichlorvos exposure: crosstalk between mitochondrial impairments, alpha synuclein aggregation, oxidative damage and behavioral changes. Mol Brain 3: 35.
11. Jankovic J, Poewe W (2012) Therapies in Parkinson's disease. Curr Opin Neurol 25: 433-447.
12. Yi L, Liang Y, Wu H, Yuan D (2009) The analysis of Radix Angelicae Sinensis (Danggui). J Chromatogr A 1216: 1991-2001.
13. Chiu SC, Chen SP, Huang SY, Wang MJ, Lin SZ, et al. (2012) Induction of apoptosis coupled to endoplasmic reticulum stress in human prostate cancer cells by n-butylidenephthalide. PLoS One 7: e33742.
14. Wei CW, Lin CC, Yu YL, Lin CY, Lin PC, et al. (2009) n- Butylidenephthalide induced apoptosis in the A549 human lung adenocarcinoma cell line by coupled down-regulation of AP-2alpha and telomerase activity. Acta Pharmacol Sin 30: 1297-1306.
15. Chen YL, Jian MH, Lin CC, Kang JC, Chen SP, et al. (2008) The induction of orphan nuclear receptor Nur77 expression by n-butylenephthalide as pharmaceuticals on hepatocellular carcinoma cell therapy. Mol Pharmacol 74: 1046-1058.
16. Yeh JC, Cindrova-Davies T, Belleri M, Morbidelli L, Miller N, et al. (2011) The natural compound n-butylidenephthalide derived from the volatile oil of Radix Angelica sinensis inhibits angiogenesis in vitro and in vivo. Angiogenesis 14: 187-197.
17. Fu RH, Hran HJ, Chu CL, Huang CM, Liu SP, et al. (2011) Lipopolysaccharide-stimulated activation of murine DC2.4 cells is attenuated by n-butylidenephthalide through suppression of the NF-kappaB pathway. Biotechnol Lett 33: 903-910.
18. Teng CM, Chen WY, Ko WC, Ouyang CH (1987) Antiplatelet effect of butylidenephthalide. Biochim Biophys Acta 924: 375-382. (Pubitemid 17090241)
19. Ko WC, Liao CC, Shih CH, Lei CB, Chen CM (2002) Relaxant effects of butylidenephthalide in isolated dog blood vessels. Planta Med 68: 1004-1009. (Pubitemid 35448995)
20. Chan SS, Choi AO, Jones RL, Lin G (2006) Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta. Eur J Pharmacol 537: 111-117.
21. Chan SS, Jones RL, Lin G (2009) Synergistic interaction between the Ligusticum chuanxiong constituent butylidenephthalide and the nitric oxide donor sodium nitroprusside in relaxing rat isolated aorta. J Ethnopharmacol 122: 308-312.
22. Ko WC, Sheu JR, Tzeng SH, Chen CM (1998) The selective antianginal effect without changing blood pressure of butylidenephthalide in conscious rats. Planta Med 64: 229-232.
23. Ko WC, Charng CY, Sheu JR, Tzeng SH, Chen CM (1998) Effect of butylidenephthalide on calcium mobilization in isolated rat aorta. J Pharm Pharmacol 50: 1365-1369.
24. Mimura Y, Kobayashi S, Naitoh T, Kimura I, Kimura M (1995) The structure-activity relationship between synthetic butylidenephthalide derivatives regarding the competence and progression of inhibition in primary cultures proliferation of mouse aorta smooth muscle cells. Biol Pharm Bull 18: 1203-1206.
25. Harrington AJ, Yacoubian TA, Slone SR, Caldwell KA, Caldwell GA (2012) Functional analysis of VPS41-mediated neuroprotection in Caenorhabditis elegans and mammalian models of Parkinson's disease. J Neurosci 32: 2142-2153.
26. Kuwahara T, Tonegawa R, Ito G, Mitani S, Iwatsubo T (2012) Phosphorylation of alpha-synuclein protein at Ser-129 reduces neuronal dysfunction by lowering its membrane binding property in Caenorhabditis elegans. J Biol Chem 287: 7098-7109.
27. Jadiya P, Chatterjee M, Sammi SR, Kaur S, Palit G, et al. (2011) Sir-2.1 modulates 'calorie-restriction-mediated' prevention of neurodegeneration in Caenorhabditis elegans: implications for Parkinson's disease. Biochem Biophys Res Commun 413: 306-310.
28. Liu Z, Hamamichi S, Lee BD, Yang D, Ray A, et al. (2011) Inhibitors of LRRK2 kinase attenuate neurodegeneration and Parkinson-like phenotypes in Caenorhabditis elegans and Drosophila Parkinson's disease models. Hum Mol Genet 20: 3933-3942.
29. Schreiber MA, McIntire SL (2011) A Caenorhabditis elegans p38 MAP kinase pathway mutant protects from dopamine, methamphetamine, and MDMA toxicity. Neurosci Lett 498: 99-103.
30. Martinez-Finley EJ, Avila DS, Chakraborty S, Aschner M (2011) Insights from Caenorhabditis elegans on the role of metals in neurodegenerative diseases. Metallomics 3: 271-279.
31. Benedetto A, Au C, Avila DS, Milatovic D, Aschner M (2010) Extracellular dopamine potentiates mn-induced oxidative stress, lifespan reduction, and dopaminergic neurodegeneration in a BLI-3-dependent manner in Caenorhabditis elegans. PLoS Genet 6: e1001084.
32. Yao C, El Khoury R, Wang W, Byrd TA, Pehek EA, et al. (2010) LRRK2-mediated neurodegeneration and dysfunction of dopaminergic neurons in a Caenorhabditis elegans model of Parkinson's disease. Neurobiol Dis 40: 73-81.
33. Kamp F, Exner N, Lutz AK, Wender N, Hegermann J, et al. (2010) Inhibition of mitochondrial fusion by alpha-synuclein is rescued by PINK1, Parkin and DJ-1. EMBO J 29: 3571-3589.
34. Cornejo Castro EM, Waak J, Weber SS, Fiesel FC, Oberhettinger P, et al. (2010) Parkinson's disease-associated DJ-1 modulates innate immunity signaling in Caenorhabditis elegans. J Neural Transm 117: 599-604.
35. Asikainen S, Rudgalvyte M, Heikkinen L, Louhiranta K, Lakso M, et al. (2010) Global microRNA expression profiling of Caenorhabditis elegans Parkinson's disease models. J Mol Neurosci 41: 210-218.
36. Roodveldt C, Bertoncini CW, Andersson A, van der Goot AT, Hsu ST, et al. (2009) Chaperone proteostasis in Parkinson's disease: stabilization of the Hsp70/alpha-synuclein complex by Hip. EMBO J 28: 3758-3770.
37. Ruan Q, Harrington AJ, Caldwell KA, Caldwell GA, Standaert DG (2010) VPS41, a protein involved in lysosomal trafficking, is protective in Caenorhabditis elegans and mammalian cellular models of Parkinson's disease. Neurobiol Dis 37: 330-338.
38. Caldwell KA, Tucci ML, Armagost J, Hodges TW, Chen J, et al. (2009) Investigating bacterial sources of toxicity as an environmental contributor to dopaminergic neurodegeneration. PLoS One 4: e7227.
39. Bargmann CI (1998) Neurobiology of the Caenorhabditis elegans genome. Science 282: 2028-2033.
40. van der Goot AT, Zhu W, Vazquez-Manrique RP, Seinstra RI, Dettmer K, et al. (2012) Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation. Proc Natl Acad Sci U S A 109: 14912-14917.
41. Lee JY, Song J, Kwon K, Jang S, Kim C, et al. (2012) Human DJ-1 and its homologs are novel glyoxalases. Hum Mol Genet 21: 3215-3225.
42. Zheng M, Gorelenkova O, Yang J, Feng Z (2012) A liquid phase based C. elegans behavioral analysis system identifies motor activity loss in a nematode Parkinson's disease model. J Neurosci Methods 204: 234-237.
43. Vidal-Gadea AG, Pierce-Shimomura JT (2012) Conserved role of dopamine in the modulation of behavior. Commun Integr Biol 5: 440-447.
44. Kuwahara T, Koyama A, Koyama S, Yoshina S, Ren CH, et al. (2008) A systematic RNAi screen reveals involvement of endocytic pathway in neuronal dysfunction in alpha-synuclein transgenic C. elegans. Hum Mol Genet 17: 2997-3009.
45. Tucci ML, Harrington AJ, Caldwell GA, Caldwell KA (2011) Modeling dopamine neuron degeneration in Caenorhabditis elegans. Methods Mol Biol 793: 129-148.
46. De Jesus-Cortes H, Xu P, Drawbridge J, Estill SJ, Huntington P, et al. (2012) Neuroprotective efficacy of aminopropyl carbazoles in a mouse model of Parkinson disease. Proc Natl Acad Sci U S A 109: 17010-17015.
47. Cao P, Yuan Y, Pehek EA, Moise AR, Huang Y, et al. (2010) Alpha-synuclein disrupted dopamine homeostasis leads to dopaminergic neuron degeneration in Caenorhabditis elegans. PLoS One 5: e9312.
48. Slone SR, Lesort M, Yacoubian TA (2011) 14-3-3theta protects against neurotoxicity in a cellular Parkinson's disease model through inhibition of the apoptotic factor Bax. PLoS One 6: e21720.
49. Harrington AJ, Knight AL, Caldwell GA, Caldwell KA (2011) Caenorhabditis elegans as a model system for identifying effectors of alpha-synuclein misfolding and dopaminergic cell death associated with Parkinson's disease. Methods 53: 220-225.
50. Yacoubian TA, Slone SR, Harrington AJ, Hamamichi S, Schieltz JM, et al. (2010) Differential neuroprotective effects of 14-3-3 proteins in models of Parkinson's disease. Cell Death Dis 1: e2.
51. Jadiya P, Khan A, Sammi SR, Kaur S, Mir SS, et al. (2011) Anti-Parkinsonian effects of Bacopa monnieri: insights from transgenic and pharmacological Caenorhabditis elegans models of Parkinson's disease. Biochem Biophys Res Commun 413: 605-610.
52. Locke CJ, Fox SA, Caldwell GA, Caldwell KA (2008) Acetaminophen attenuates dopamine neuron degeneration in animal models of Parkinson's disease. Neurosci Lett 439: 129-133.
53. Fu RH, Wang YC, Chen CS, Tsai RT, Liu SP, et al. (2013) Acetylcorynoline attenuates dopaminergic neuron degeneration and alpha-synuclein aggregation in animal models of Parkinson's disease. Neuropharmacology doi:10.1016/j. neuropharm.2013.08.007.
54. Brenner S (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71-94.
55. Yang X, Zhang P, Wu J, Xiong S, Jin N, et al. (2012) The neuroprotective and lifespan-extension activities of Damnacanthus officinarum extracts in Caenorhabditis elegans. J Ethnopharmacol 141: 41-47.
56. Voisine C, Varma H, Walker N, Bates EA, Stockwell BR, et al. (2007) Identification of potential therapeutic drugs for huntington's disease using Caenorhabditis elegans. PLoS One 2: e504.
57. Nass R, Hall DH, Miller DM 3rd, Blakely RD (2002) Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans. Proc Natl Acad Sci U S A 99: 3264-3269. (Pubitemid 34240620)
58. Sawin ER, Ranganathan R, Horvitz HR (2000) C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron 26: 619-631.
59. Kuwahara T, Koyama A, Gengyo-Ando K, Masuda M, Kowa H, et al. (2006) Familial Parkinson mutant alpha-synuclein causes dopamine neuron dysfunction in transgenic Caenorhabditis elegans. J Biol Chem 281: 334-340. (Pubitemid 43671193)
60. Hoogewijs D, Houthoofd K, Matthijssens F, Vandesompele J, Vanfleteren JR (2008) Selection and validation of a set of reliable reference genes for quantitative sod gene expression analysis in C. elegans. BMC Mol Biol 9: 9.
61. Vilchez D, Morantte I, Liu Z, Douglas PM, Merkwirth C, et al. (2012) RPN-6 determines C. elegans longevity under proteotoxic stress conditions. Nature 489: 263-268.
62. Shvadchak VV, Yushchenko DA, Pievo R, Jovin TM (2011) The mode of alpha-synuclein binding to membranes depends on lipid composition and lipid to protein ratio. FEBS Lett 585: 3513-3519.
63. Bove J, Perier C (2012) Neurotoxin-based models of Parkinson's disease. Neuroscience 211: 51-76.
64. Saw CL, Wu Q, Su ZY, Wang H, Yang Y, et al. (2013) Effects of natural phytochemicals in Angelica sinensis (Danggui) on Nrf2-mediated gene expression of phase II drug metabolizing enzymes and anti-inflammation. Biopharm Drug Dispos DOI: 10.1002/bdd.1846.
65. Hwang CK, Chun HS (2012) Isoliquiritigenin isolated from licorice Glycyrrhiza uralensis prevents 6-hydroxydopamine-induced apoptosis in dopaminergic neurons. Biosci Biotechnol Biochem 76: 536-543.
66. Charriaut-Marlangue C (2004) Apoptosis: a target for neuroprotection. Therapie 59: 185-190.
67. Pourkarimi E, Greiss S, Gartner A (2012) Evidence that CED-9/Bcl2 and CED-4/Apaf-1 localization is not consistent with the current model for C. elegans apoptosis induction. Cell Death Differ 19: 406-415.
68. Hyman BT, Yuan J (2012) Apoptotic and non-apoptotic roles of caspases in neuronal physiology and pathophysiology. Nat Rev Neurosci 13: 395-406.
69. van Ham TJ, Thijssen KL, Breitling R, Hofstra RM, Plasterk RH, et al. (2008) C. elegans model identifies genetic modifiers of alpha-synuclein inclusion formation during aging. PLoS Genet 4: e1000027.
70. Hamamichi S, Rivas RN, Knight AL, Cao S, Caldwell KA, et al. (2008) Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model. Proc Natl Acad Sci U S A 105: 728-733. (Pubitemid 351171776)
71. Karpinar DP, Balija MB, Kugler S, Opazo F, Rezaei-Ghaleh N, et al. (2009) Pre-fibrillar alpha-synuclein variants with impaired beta-structure increase neurotoxicity in Parkinson's disease models. EMBO J 28: 3256-3268.
72. Usenovic M, Knight AL, Ray A, Wong V, Brown KR, et al. (2012) Identification of novel ATP13A2 interactors and their role in alpha-synuclein misfolding and toxicity. Hum Mol Genet 21: 3785-3794.
73. van Ham TJ, Holmberg MA, van der Goot AT, Teuling E, Garcia-Arencibia M, et al. (2010) Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity. Cell 142: 601-612.
74. Nedelsky NB, Todd PK, Taylor JP (2008) Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection. Biochim Biophys Acta 1782: 691-699.
75. Yu Z, Kleifeld O, Lande-Atir A, Bsoul M, Kleiman M, et al. (2011) Dual function of Rpn5 in two PCI complexes, the 26S proteasome and COP9 signalosome. Mol Biol Cell 22: 911-920.
76. Maccarrone M, Bernardi G, Agro AF, Centonze D (2011) Cannabinoid receptor signalling in neurodegenerative diseases: a potential role for membrane fluidity disturbance. Br J Pharmacol 163: 1379-1390.
77. Sebastiao AM, Colino-Oliveira M, Assaife-Lopes N, Dias RB, Ribeiro JA (2013) Lipid rafts, synaptic transmission and plasticity: impact in age-related neurodegenerative diseases. Neuropharmacology 64: 97-107.
78. Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol 8: 382-397.
79. Rogers J, Mastroeni D, Leonard B, Joyce J, Grover A (2007) Neuroinflammation in Alzheimer's disease and Parkinson's disease: are microglia pathogenic in either disorder? Int Rev Neurobiol 82: 235-246.
80. Collins LM, Toulouse A, Connor TJ, Nolan YM (2012) Contributions of central and systemic inflammation to the pathophysiology of Parkinson's disease. Neuropharmacology 62: 2154-2168.
81. Kim HG, Ju MS, Ha SK, Lee H, Kim SY, et al. (2012) Acacetin protects dopaminergic cells against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neuroinflammation in vitro and in vivo. Biol Pharm Bull 35: 1287-1294.
82. Du XX, Xu HM, Jiang H, Song N, Wang J, et al. (2012) Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson's disease. Neurosci Bull 28: 253-258.
83. Kumar H, Kim IS, More SV, Kim BW, Bahk YY, et al. (2013) Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson's disease model. Evid Based Complement Alternat Med 2013: 514095.
84. Zhang ZJ, Cheang LC, Wang MW, Lee SM (2011) Quercetin exerts a neuroprotective effect through inhibition of the iNOS/NO system and proinflammation gene expression in PC12 cells and in zebrafish. Int J Mol Med 27: 195-203.
85. Lu JH, Tan JQ, Durairajan SS, Liu LF, Zhang ZH, et al. (2012) Isorhynchophylline, a natural alkaloid, promotes the degradation of alpha-synuclein in neuronal cells via inducing autophagy. Autophagy 8: 98-108.
86. Zbarsky V, Datla KP, Parkar S, Rai DK, Aruoma OI, et al. (2005) 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 39: 1119-1125. (Pubitemid 41358566)
87. Ramassamy C (2006) Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 545: 51-64.
88. Pandey N, Strider J, Nolan WC, Yan SX, Galvin JE (2008) Curcumin inhibits aggregation of alpha-synuclein. Acta Neuropathol 115: 479-489.
89. Ahmad B, Lapidus LJ (2012) Curcumin prevents aggregation in alpha-synuclein by increasing reconfiguration rate. J Biol Chem 287: 9193-9199.
90. Berman AE, Chan WY, Brennan AM, Reyes RC, Adler BL, et al. (2011) N-acetylcysteine prevents loss of dopaminergic neurons in the EAAC1-/- mouse. Ann Neurol 69: 509-520.
91. Clark J, Clore EL, Zheng K, Adame A, Masliah E, et al. (2010) Oral N-acetylcysteine attenuates loss of dopaminergic terminals in alpha-synuclein overexpressing mice. PLoS One 5: e12333.
92. Etminan M, Gill SS, Samii A (2005) Intake of vitamin E, vitamin C, and carotenoids and the risk of Parkinson's disease: a meta-analysis. Lancet Neurol 4: 362-365. (Pubitemid 40720032)
93. Tsai NM, Chen YL, Lee CC, Lin PC, Cheng YL, et al. (2006) The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo. J Neurochem 99: 1251-1262.
94. Tan W, Li Y, Chen M, Wang Y (2011) Berberine hydrochloride: anticancer activity and nanoparticulate delivery system. Int J Nanomedicine 6: 1773-1777.
95. Onishi H, Machida Y (2005) Macromolecular and nanotechnological modification of camptothecin and its analogs to improve the efficacy. Curr Drug Discov Technol 2: 169-183. (Pubitemid 41242962)
96. Fu RH, Liu SP, Ou CW, Huang CM, Wang YC (2010) Spatial control of cells, peptide delivery and dynamic monitoring of cellular physiology with chitosan-assisted dual color quantum dot FRET peptides. Acta Biomater 6: 3621-3629.