Caffeic acid phenethyl ester (CAPE) prevents transformation of human cells by arsenite (As) and suppresses growth of As-transformed cells
- 作者：Chengfeng Yang ; Jing Wu ; Ronghe Zhang ; Ping Zhang ; Jonathan Eckard ; Rita Yusuf ; Xi Huang ; Toby G. Rossman and Krystyna Frenkel
- 关键词：Apoptosis ; Cdc2 ; Cyclin B1 ; Inflammatory cytokines ; EGCG ; G2/M interphase ; Cell growth arrest ; Gene and protein arrays ; Prevention ; Resveratrol
- 刊名：Toxicology
- 出版年：2005
- 期刊代码：47_0300483x
- 类别：pha
- 出版时间：2005
- 卷：213
- 期：1-2
- 页码：81-96
- 文件大小：358 K
摘要
Recent evidence suggests that inflammatory cytokines and growth factors contribute to arsenite (As)-induced human carcinogenesis. We investigated the expression of inflammatory cytokine mRNAs during the transformation process induced by chronic As exposure in non-tumorigenic human osteogenic sarcoma (N-HOS) cells using gene arrays, and results were confirmed by RT-PCR and protein arrays. Caffeic acid phenethyl ester (CAPE), a naturally occurring immunomodulating agent, was used to evaluate the role of inflammatory factors in the process of As-mediated N-HOS cell transformation and in As-transformed HOS (AsT-HOS) cells. We found that an 8-week continuous exposure of N-HOS to 0.3 μM arsenite resulted in HOS cell transformation. That exposure also caused substantial decreases in inflammatory cytokine mRNAs, such as interleukin (IL) IL-1α, IL-2, IL-8, IL-18, MCP-1, TGF-β2, and TNF-α, while it increased c-jun mRNA in a time-dependent manner. Co-incubation of N-HOS with As and CAPE (0.5–2.5 μM) prevented As-mediated declines in cytokine mRNAs in the co-treated cells, as well as their transformation to anchorage independence, while it caused decreases in c-jun mRNA. CAPE (up to 10 μM) had no effect on growth of N-HOS cells. However, CAPE (1–10 μM) treatment of AsT-HOS cells inhibited cell growth, induced cell cycle G2/M arrest, and triggered apoptosis, accompanied by changes in cytokine gene expression, as well as decreases in cyclin B1 and cdc2 abundance. Resveratrol (RV) and (−)
epigallocatechin gallate (EGCG), preventive agents present in grapes and green tea, respectively, induced similar changes in AsT-HOS cell growth but required much higher doses than CAPE to cause 50%growth arrest (<2.5 μM CAPE versus 25 μM RV or 50 μM EGCG). Overall, our findings suggest that inflammatory cytokines play an important role in the suppressive effects of CAPE on As-induced cell transformation and in the selective cytotoxicity of CAPE to As-transformed HOS cells.
epigallocatechin gallate (EGCG), preventive agents present in grapes and green tea, respectively, induced similar changes in AsT-HOS cell growth but required much higher doses than CAPE to cause 50%growth arrest (<2.5 μM CAPE versus 25 μM RV or 50 μM EGCG). Overall, our findings suggest that inflammatory cytokines play an important role in the suppressive effects of CAPE on As-induced cell transformation and in the selective cytotoxicity of CAPE to As-transformed HOS cells.