title: Honokiol suppresses metastasis of renal cell carcinoma by targeting KISS1/KISS1R signaling.
abstract: Renal cell carcinoma (RCC) is a common urological cancer worldwide and is known to have a high risk of metastasis, which is considered responsible for more than 90% of cancer associated deaths. Honokiol is a small-molecule biphenol isolated from Magnolia spp. bark and has been shown to be a potential anticancer agent involved in multiple facets of signal transduction. In this study, we demonstrated that honokiol inhibited the invasion and colony formation of highly metastatic RCC cell line 786-0 in a dose-dependent manner. DNA-microarray data showed the significant upregulation of metastasis-suppressor gene KISS1 and its receptor, KISS1R. The upregulation was confirmed by qRT-PCR analysis. Overexpression of KISS1 and KISS1R was detected by western blotting at the translation level as well. Of note, the decreased invasive and colonized capacities were reversed by KISS1 knockdown. Taken together, the results first indicate that activation of KISS1/KISS1R signaling by honokiol suppresses multistep process of metastasis, including invasion and colony formation, in RCC cells 786-0. Honokiol may be considered as a natural agent against RCC metastasis.
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, USA.
authors.forename: Shujie
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Castillo
authors.affiliation: Amitabha Medical Clinic and Healing Center, Santa Rosa, CA, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Eliaz
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indiana University Health, Indianapolis, IN, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sliva
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D059648:Kisspeptins / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D015398:Signal Transduction / Q000187:drug effects*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D059648:Kisspeptins; D017705:Lignans; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; C106628:KISS1 protein, human; C118688:KISS1R protein, human; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
references.citation: Mol Oncol. 2014 May;8(3):565-80
references.pmid: 24508063
references.citation: Future Oncol. 2014 May;10(6):1095-111
references.pmid: 24941992
references.citation: Curr Mol Med. 2012 Dec;12(10):1244-52
references.pmid: 22834827
references.citation: J Pathol. 2011 Jan;223(1):46-53
references.pmid: 20922711
references.citation: Eur Urol. 2009 Feb;55(2):441-9
references.pmid: 18395325
references.citation: Nutr Cancer. 2004;49(2):209-16
references.pmid: 15489214
references.citation: PLoS One. 2013;8(4):e60749
references.pmid: 23580348
references.citation: Int J Oncol. 2012 Oct;41(4):1358-64
references.pmid: 22895699
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Chem Biol Interact. 2014 Sep 25;221:13-23
references.pmid: 25106108
references.citation: Mol Cells. 2014 May;37(5):383-8
references.pmid: 24810210
references.citation: Anticancer Drugs. 2013 Jul;24(6):535-54
references.pmid: 23552469
references.citation: Oncol Lett. 2013 Nov;6(5):1435-1438
references.pmid: 24179537
references.citation: Med Oncol. 2006;23(2):245-50
references.pmid: 16720925
references.citation: Drug Discov Ther. 2013 Jun;7(3):109-15
references.pmid: 23917859
references.citation: Nat Rev Genet. 2007 May;8(5):341-52
references.pmid: 17440531
references.citation: J Urol. 2012 Dec;188(6):2095-100
references.pmid: 23083849
references.citation: Int J Cancer. 2009 Jun 1;124(11):2709-18
references.pmid: 19219913
references.citation: Cancer Biomark. 2010;9(1-6):461-73
references.pmid: 22112490
references.citation: Biochem Biophys Res Commun. 2013 Jan 18;430(3):876-82
references.pmid: 23262230
references.citation: Int J Oncol. 2014 Jan;44(1):187-94
references.pmid: 24247297
references.citation: Oncol Rep. 2013 Jun;29(6):2318-24
references.pmid: 23525508
references.citation: Int J Oncol. 2013 Oct;43(4):1103-10
references.pmid: 23877711
references.citation: J Natl Cancer Inst. 1996 Dec 4;88(23):1731-7
references.pmid: 8944003
references.citation: PLoS One. 2011;6(4):e18490
references.pmid: 21559510
references.citation: Int J Oncol. 2013 Feb;42(2):721-32
references.pmid: 23242346
references.citation: BMC Gastroenterol. 2007;7:4
references.pmid: 17266757
references.citation: Prostate. 2014 Sep;74(12):1209-21
references.pmid: 25043291
references.citation: Int J Oncol. 2003 Nov;23(5):1277-83
references.pmid: 14532966
references.citation: Eur J Cancer. 2010 May;46(7):1283-9
references.pmid: 20303258
references.citation: J Cell Biochem. 2014 Nov;115(11):1888-99
references.pmid: 24905183
references.citation: Int J Oncol. 2014 May;44(5):1490-8
references.pmid: 24585183
references.citation: Evid Based Complement Alternat Med. 2013;2013:146136
references.pmid: 23662112
references.citation: Cancer Treat Rev. 2008 May;34(3):193-205
references.pmid: 18313224
references.citation: Nat Rev Cancer. 2006 Jun;6(6):449-58
references.pmid: 16723991
references.citation: Cancer Metastasis Rev. 2010 Sep;29(3):447-63
references.pmid: 20714788
references.citation: Carcinogenesis. 2013 Nov;34(11):2568-79
references.pmid: 23828905
references.citation: Eur J Cancer. 2010 May;46(7):1198-203
references.pmid: 20303259
references.citation: Int J Oncol. 2011 Mar;38(3):769-76
references.pmid: 21225228
references.citation: Nature. 2001 May 31;411(6837):613-7
references.pmid: 11385580
references.citation: Life Sci. 2008 Aug 29;83(9-10):332-8
references.pmid: 18644390
references.citation: PLoS One. 2012;7(8):e43711
references.pmid: 22937084
references.citation: Urology. 2012 Dec;80(6):1298-302.e1
references.pmid: 23206776
references.citation: Br J Cancer. 2013 Jul 23;109(2):433-43
references.pmid: 23807168
references.citation: Int Rev Cell Mol Biol. 2011;286:107-80
references.pmid: 21199781
references.citation: PLoS One. 2014;9(2):e86369
references.pmid: 24586249
references.citation: Int J Oncol. 2013 Jun;42(6):1869-74
references.pmid: 23588713
references.citation: J Cancer. 2013 Sep 26;4(8):653-61
references.pmid: 24155777
references.citation: Cancer. 2007 Apr 1;109(7):1279-89
references.pmid: 17326044