Abstract | PURPOSE: The anti- lung cancer effect of Cryptomeria japonica leaf extractive and its active phytocompound was evaluated using in vitro and in vivo assays. EXPERIMENTAL DESIGN: The anti- lung cancer mechanism was investigated using flow cytometry and western blot analyses, and the antitumor activity was evaluated in a xenograft animal model. RESULTS: MTT assay indicated that the cytotoxic effects of ferruginol in A549 and CL1-5 cells were dose-dependent. According to the results of cell cycle and annexin V/PI analyses, the sub-G1 population and annexin V binding in the 2 cell lines were increased after ferruginol treatment. The results of western blot analyses revealed that the cleaved forms of caspase 3, 8, 9, and poly(ADP-ribose) polymerase were activated after ferruginol treatment in A549 and CL1-5 cells. Moreover, the expression of the anti-apoptotic protein Bcl-2 was decreased, while the expression of the pro-apoptotic protein Bax was elevated, after ferruginol treatment in both lung cancer cell lines. These results indicated that ferruginol acted via a caspase-dependent mitochondrial apoptotic pathway in the 2 cell lines. Intraperitoneal administration of ferruginol significantly suppressed the growth of subcutaneous CL1-5 xenografts. CONCLUSIONS: The findings of the present study provided insight into the molecular mechanisms underlying ferruginol-induced apoptosis in non-small cell lung cancer (NSCLC) cells, indicating that this compound may be a potential candidate drug for anti-NSCLC.
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Authors | Shang-Tse Ho, Yu-Tang Tung, Yueh-Hsiung Kuo, Chi-Chen Lin, Jyh-Horng Wu |
Journal | Integrative cancer therapies
(Integr Cancer Ther)
Vol. 14
Issue 1
Pg. 86-97
(Jan 2015)
ISSN: 1552-695X [Electronic] United States |
PMID | 25355727
(Publication Type: Journal Article)
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Copyright | © The Author(s) 2014. |
Chemical References |
- Abietanes
- Antineoplastic Agents, Phytogenic
- Proto-Oncogene Proteins c-bcl-2
- bcl-2-Associated X Protein
- ferruginol
- Caspases
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Topics |
- Abietanes
(pharmacology)
- Animals
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Blotting, Western
- Carcinoma, Non-Small-Cell Lung
(drug therapy, enzymology, pathology)
- Caspases
(metabolism)
- Cryptomeria
(chemistry)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Flow Cytometry
- Humans
- Injections, Intraperitoneal
- Lung Neoplasms
(drug therapy, enzymology, pathology)
- Mice
- Phytotherapy
- Plant Leaves
(chemistry)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Tumor Cells, Cultured
- bcl-2-Associated X Protein
(metabolism)
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