Ferruginol inhibits non-small cell lung cancer growth by inducing caspase-associated apoptosis.

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.

• 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)
• Copyright: © The Author(s) 2014.

Chemical References

• Abietanes
• Antineoplastic Agents, Phytogenic
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• ferruginol
• Caspases

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)