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

Shang Tse Ho, Yu Tang Tung, Yueh Hsiung Kuo, Chi Chen Lin, Jyh Horng Wu

Research output: Contribution to journalArticle

10 Citations (Scopus)

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(ADPribose) 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.

Original languageEnglish
Pages (from-to)86-97
Number of pages12
JournalIntegrative Cancer Therapies
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 19 2015
Externally publishedYes

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Caspases
Non-Small Cell Lung Carcinoma
Apoptosis
Growth
Lung Neoplasms
Apoptosis Regulatory Proteins
Annexin A5
Heterografts
Cell Line
Western Blotting
Cryptomeria
Poly(ADP-ribose) Polymerases
Caspase 8
ferruginol
Caspase 3
Cell Cycle
Flow Cytometry
Research Design
Animal Models
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Caspase
  • Cryptomeria japonica
  • Ferruginol
  • Lung cancer
  • NSCLC
  • Phytocompound

ASJC Scopus subject areas

  • Oncology
  • Complementary and alternative medicine

Cite this

Ferruginol inhibits non-small cell lung cancer growth by inducing caspase-associated apoptosis. / Ho, Shang Tse; Tung, Yu Tang; Kuo, Yueh Hsiung; Lin, Chi Chen; Wu, Jyh Horng.

In: Integrative Cancer Therapies, Vol. 14, No. 1, 19.01.2015, p. 86-97.

Research output: Contribution to journalArticle

Ho, Shang Tse ; Tung, Yu Tang ; Kuo, Yueh Hsiung ; Lin, Chi Chen ; Wu, Jyh Horng. / Ferruginol inhibits non-small cell lung cancer growth by inducing caspase-associated apoptosis. In: Integrative Cancer Therapies. 2015 ; Vol. 14, No. 1. pp. 86-97.
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