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Int. J. Mol. Sci. 2015, 16(2), 2717-2731; doi:10.3390/ijms16022717

Myricanol Induces Apoptotic Cell Death and Anti-Tumor Activity in Non-Small Cell Lung Carcinoma in Vivo

1,2,†,* , 1,†
,
1
,
1
,
2
,
1
and
2,3,*
1
Institute of Basic Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China
2
Institute of Cancer Research, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310007, China
3
Oncology Department, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Maurizio Battino
Received: 25 November 2014 / Accepted: 21 January 2015 / Published: 26 January 2015
View Full-Text   |   Download PDF [12919 KB, uploaded 26 January 2015]   |  

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. View Full-Text
Keywords: myricanol; anticancer; A549 xenograft; immunohistochemistry; TUNEL assay; apoptosis myricanol; anticancer; A549 xenograft; immunohistochemistry; TUNEL assay; apoptosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Dai, G.; Tong, Y.; Chen, X.; Ren, Z.; Ying, X.; Yang, F.; Chai, K. Myricanol Induces Apoptotic Cell Death and Anti-Tumor Activity in Non-Small Cell Lung Carcinoma in Vivo. Int. J. Mol. Sci. 2015, 16, 2717-2731.

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