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Myricanol induces apoptotic cell death and anti-tumor activity in non-small cell lung carcinoma in vivo.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2015 Jan 26; Vol. 16 (2), pp. 2717-31. Date of Electronic Publication: 2015 Jan 26. - Publication Year :
- 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.
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents therapeutic use
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung metabolism
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Diarylheptanoids chemistry
Diarylheptanoids therapeutic use
Humans
Hypoxia-Inducible Factor 1, alpha Subunit genetics
Hypoxia-Inducible Factor 1, alpha Subunit metabolism
Immunohistochemistry
Inhibitor of Apoptosis Proteins genetics
Inhibitor of Apoptosis Proteins metabolism
Lung Neoplasms drug therapy
Lung Neoplasms metabolism
Lung Neoplasms pathology
Mice
Mice, Nude
Polyethylene Glycols chemistry
Survivin
Up-Regulation drug effects
Vascular Endothelial Growth Factor A genetics
Vascular Endothelial Growth Factor A metabolism
Xenograft Model Antitumor Assays
bcl-2-Associated X Protein genetics
bcl-2-Associated X Protein metabolism
Antineoplastic Agents pharmacology
Apoptosis drug effects
Diarylheptanoids pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 16
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 25629230
- Full Text :
- https://doi.org/10.3390/ijms16022717