Chan-Yu-Bao-Yuan-Tang induces apoptosis in NSCLC and SCLC cell lines via a mitochondria-mediated pathway

Abstract

1. Previous clinical studies have shown efficacy and safety of the traditional Chinese medicinal herb extract Chan-Yu-Bao-Yuan-Tang (CYBYT) in lung cancer patients.

2. The effects of CYBYT on proliferation and apoptosis in the non-small cell lung cancer cell line NCI-H460 and the small cell lung cancer cell line NCI-H446 were investigated in vitro.

3. CYBYT significantly induced antiproliferative effects of NCI-H460 and NCI-H446 cells in a concentration- and time-dependent manner. The IC₅₀ values in NCI-H460 cells were 94.37 µg/mL (24 h) and 20.89 µg/mL (48 h), whereas in NCI-H446 cells IC₅₀ values were 214.72 µg/mL (24 h) and 114.58 µg/mL (48 h). Annexin V–FITC/PI staining showed CYBYT could significantly induce apoptosis in NCI-H460 and NCI-H446 cells, and the total apoptosis rates were positively correlated with the concentration and time of CYBYT treatment. Furthermore, treatment with the broad-spectrum caspase inhibitor (z-VAD-fmk) effectively protected NCI-H460 and NCI-H446 cells against CYBYT-triggered apoptosis. The apoptotic processes involved were a marked decrease in antiapoptotic protein Bcl-2 and an increase in proapoptotic protein Bax. The release of mitochondrial cytochrome c into the cytosol was also observed, which, in turn, resulted in the activation of caspase-9 and caspase-3.

4. CYBYT exerts antiproliferative and growth inhibition effects on NCI-H460 and NCI-H446 cells through the mitochondrial caspase-dependent cell death pathway.

Keywords::

• CYBYT
• apoptosis
• proliferation
• mitochondria
• NSCLC
• SCLC

Acknowledgements

This work was supported by the grant from the Administration Bureau of Traditional Chinese Medicine of Zhejiang Province, China (No. 2008CA113) and Zhoushan Municipal Health Bureau of Zhejiang Province, China (No. 2008A001 and 06G01), and the Program for New Century Excellent Talents at the University of China (2007).

Declaration of interest

The authors report no declarations of interest.