Growth inhibitory and apoptosis-inducing effects of allergen-free Rhus verniciflua Stokes extract on A549 human lung cancer cells

Jang,Ik-Soon; Park,Jae-Woo; Jo,Eun-Bi; Cho,Chong-Kwan; Lee,Yeon-Weol; Yoo,Hwa‑Seung; Park,Junsoo; Kim,Jihye; Jang,Byeong-Churl; Choi,Jong-Soon

doi:10.3892/or.2016.5131

Growth inhibitory and apoptosis-inducing effects of allergen-free Rhus verniciflua Stokes extract on A549 human lung cancer cells

Authors:
- Ik-Soon Jang
- Jae-Woo Park
- Eun-Bi Jo
- Chong-Kwan Cho
- Yeon-Weol Lee
- Hwa‑Seung Yoo
- Junsoo Park
- Jihye Kim
- Byeong-Churl Jang
- Jong-Soon Choi
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Affiliations: Division of Bioconvergence, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea, East-West Cancer Center, Daejeon University, Daejeon 302-120, Republic of Korea, Division of Biological Science and Technology, Yonsei University, Wonju 220-100, Republic of Korea, Department of Molecular Medicine, College of Medicine, Keimyung University, Daegu 704-701, Republic of Korea
Published online on: September 23, 2016 https://doi.org/10.3892/or.2016.5131
Pages: 3037-3043

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Abstract

Evidence suggests that Rhus verniciflua Stokes (RVS) or its extract has the potential to be used for the treatment of inflammatory and neoplastic diseases. However, direct use of RVS or its extract as a herbal medicine has been limited due to the presence of urushiol, an allergenic toxin. In the present study, we prepared an extract of the allergen‑removed RVS (aRVS) based on a traditional method and investigated its inhibitory effect on the growth of various types of human cancer cells, including lung (A549), breast (MCF-7) and prostate (DU-145) cancer cell lines. Notably, among the cell lines tested, treatment with the aRVS extract strongly inhibited proliferation of the A549 cells at a 0.5 mg/ml concentration for 24 h that was not cytotoxic to normal human dermal fibroblasts. Furthermore, aRVS extract treatment largely reduced the survival and induced apoptosis of the A549 cells. At the mechanistic levels, treatment with the aRVS extract led to the downregulation of Bcl-2 and Mcl-1 proteins, the activation of caspase-9/-3 proteins, an increase in cytosolic cytochrome c levels, the upregulation of Bax protein, an increase in phosphorylated p53 protein but a decrease in phosphorylated S6 protein in the A549 cells. Importantly, treatment with z-VAD‑fmk, a pan-caspase inhibitor attenuated aRVS extract-induced apoptosis in the A549 cells. These results demonstrate firstly that aRVS extract has growth inhibitory and apoptosis-inducing effects on A549 human lung cancer cells through modulation of the expression levels and/or activities of caspases, Bcl-2, Mcl-1, Bax, p53 and S6.

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