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Integr Cancer Ther. 2015 Jan;14(1):86-97. doi: 10.1177/1534735414555806. Epub 2014 Oct 28.

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

Author information

1
National Chung Hsing University, Taichung, Taiwan.
2
China Medical University, Taichung, Taiwan.
3
National Chung Hsing University, Taichung, Taiwan eric@nchu.edu.tw lincc@nuhu.edu.tw.

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.

KEYWORDS:

Cryptomeria japonica; NSCLC; apoptosis; caspase; ferruginol; lung cancer; phytocompound

PMID:
25355727
DOI:
10.1177/1534735414555806
[Indexed for MEDLINE]

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