title: Myricanol induces apoptotic cell death and anti-tumor activity in non-small cell lung carcinoma in vivo.
abstract: This study explored the inhibiting effect and mechanism of myricanol on lung adenocarcinoma A549 xenografts in nude mice. Forty nude mice with subcutaneous A549 xenografts were randomly divided into five groups: high-dose myricanol (40 mg/kg body weight) group; middle-dose myricanol (20 mg/kg body weight) group; low-dose myricanol (10 mg/kg body weight) group; polyethylene glycol 400 vehicle group (1 mL/kg); and tumor model group. Nude mice were sacrificed after 14 days of treatment and the tumor inhibition rate (TIR, %) was then calculated. The relative mRNA expression levels of Bax, Bcl-2, VEGF, HIF-1α, and survivin in the tumor tissues were determined by real-time PCR. TUNEL assay was applied to determine cellular apoptosis, while IHC test was performed to detect the protein expression levels of Bax, Bcl-2, VEGF, HIF-1α, and survivin. The TIR of the three myricanol-treated groups ranged from 14.9% to 38.5%. The IHC results showed that the protein expression of Bcl-2, VEGF, HIF-1α, and survivin were consistently downregulated, whereas that of Bax was upregulated after myricanol treatment. Myricanol also significantly upregulated the mRNA expression of Bax and downregulated that of Bcl-2, VEGF, HIF-1α, and survivin in a dose-dependent manner (p < 0.05 to 0.001). These results are consistent with those of IHC. The TUNEL assay results indicated that apoptotic-positive cells significantly increased in the myricanol-treated tumor tissues compared with the cells of the vehicle control group (p < 0.01 to 0.001). These data suggest that myricanol could significantly decelerate tumor growth in vivo by inducing apoptosis.
authors: Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China. daiguanhai@gmail.com.
authors: Guanhai
authors: G
authors: Dai
authors: Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China. tongyeling@sina.com.
authors: Yeling
authors: Y
authors: Tong
authors: Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China. chenxuan001564@163.com.
authors: Xuan
authors: X
authors: Chen
authors: Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China. rchao007@163.com.
authors: Zeming
authors: Z
authors: Ren
authors: Institute of Cancer Research, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China. xuhuaying668@sina.com.
authors: Xuhua
authors: X
authors: Ying
authors: Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China. 88082214@163.com.
authors: Feng
authors: F
authors: Yang
authors: Institute of Cancer Research, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China. ckq3301@aliyun.com.
authors: Kequn
authors: K
authors: Chai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D036381:Diarylheptanoids / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000737:chemistry; D000077022:Survivin; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D036381:Diarylheptanoids; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C041794:myricanol; D011092:Polyethylene Glycols
references: Int J Mol Med. 2013 Aug;32(2):271-80
references: 23732337
references: Mol Cancer Res. 2014 May;12(5):728-41
references: 24523299
references: Phytomedicine. 2014 Sep 25;21(11):1490-6
references: 24939078
references: Apoptosis. 2007 Oct;12(10):1837-46
references: 17624594
references: Nat Rev Mol Cell Biol. 2008 Mar;9(3):231-41
references: 18073771
references: Blood. 2005 Jul 15;106(2):408-18
references: 15797997
references: J Cell Biol. 1997 Dec 1;139(5):1281-92
references: 9382873
references: Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7834-8
references: 7644501
references: Cell. 1993 Aug 27;74(4):609-19
references: 8358790
references: J Biol Chem. 2004 Mar 12;279(11):10331-7
references: 14681237
references: Cell Prolif. 2003 Jun;36(3):165-75
references: 12814432
references: Bioorg Med Chem. 2002 Dec;10(12):4005-12
references: 12413852
references: Biol Pharm Bull. 2001 Mar;24(3):259-63
references: 11256481
references: Phytochemistry. 2000 Aug;54(8):975-8
references: 11014300
references: Int J Mol Sci. 2013;14(8):15479-509
references: 23892596
references: Cell Signal. 2013 Sep;25(9):1895-903
references: 23707522
references: J Nat Prod. 2012 Oct 26;75(10):1798-802
references: 23066712
references: Stem Cells Dev. 2012 Sep 20;21(14):2703-17
references: 22468883
references: Biochimie. 2011 Sep;93(9):1379-91
references: 21641962
references: J Nat Prod. 2011 Jan 28;74(1):38-44
references: 21141876
references: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references: 21296855
references: Planta Med. 2010 Oct;76(14):1492-6
references: 20383816
references: Nat Prod Commun. 2009 Apr;4(4):513-6
references: 19475996
references: Med Hypotheses. 2007;69(1):33-5
references: 17280792
references: Biosci Biotechnol Biochem. 2008 Nov;72(11):3018-20
references: 18997411