Furanodiene enhances tamoxifen-induced growth inhibitory activity of ERa-positive breast cancer cells in a PPARγ independent manner

Herbal plants are enriched with compounds with a wide range of biological activities. Furanodiene is a sesquiterpene isolated from Rhizoma Curcumae. Growing evidence shows furanodiene exhibits diversified activities of hepatoprotection, anti‐inflammation, anti‐angiogenesis, and anti‐tumor. However,...

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Published in:Journal of cellular biochemistry 2012-08, Vol.113 (8), p.2643-2651
Main Authors: Zhong, Zhang-Feng, Li, Ying-Bo, Wang, Sheng-Peng, Tan, Wen, Chen, Xiu-Ping, Chen, Mei-Wan, Wang, Yi-Tao
Format: Article
Language:English
Subjects:
APOPTOSIS
Apoptosis - drug effects
Blotting, Western
BREAST CANCER
Breast Neoplasms - metabolism
CELL CYCLE
Cell Cycle - drug effects
Cell Line, Tumor
DNA Fragmentation - drug effects
Electrophoresis, Agar Gel
FURANODIENE
Furans - pharmacology
Heterocyclic Compounds, 2-Ring - pharmacology
Humans
Immunoprecipitation
PPAR gamma - metabolism
PPARγ
TAMOXIFEN
Tamoxifen - pharmacology
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Summary:Herbal plants are enriched with compounds with a wide range of biological activities. Furanodiene is a sesquiterpene isolated from Rhizoma Curcumae. Growing evidence shows furanodiene exhibits diversified activities of hepatoprotection, anti‐inflammation, anti‐angiogenesis, and anti‐tumor. However, its biological activities against breast cancer have not been deeply understood, and its potential as an anti‐breast cancer agent combined with tamoxifen (TAM) has not been evaluated so far. This study describes the combined effects of furanodiene and TAM in human breast cancer cells in vitro. The results showed that ERa‐negative MDA‐MB‐231 cells were much more sensitive than ERa‐positive MCF‐7 cells to the growth inhibition due to furanodiene. Combined administration of furanodiene and TAM led to marked increase in growth inhibition, cell cycle arrest and pro‐apoptotic activity in ERa‐positive cells compared to individual agent, and enhanced the down‐regulation of p‐cyclin D1, cyclin D1, CDK2, CDK6, p‐Rb, Rb and p‐p44, and the up‐regulation of p27, Bax and Bad, but did not show increased cytotoxicity in ERa‐negative MCF‐10A non‐tumorigenic breast epithelial cells. Co‐incubation induced the typical PARP cleavage or caspase 9 cleavages compared to individual agent. In addition, PPARγ activity inhibition by its antagonist T0070907 did not significantly reverse the enhanced effect of furanodiene and TAM suggesting that anti‐cancer properties of combination were PPARγ independent. Our data indicated that furanodiene could enhance the growth inhibitory and pro‐apoptotic activity of TAM by inducing cell cycle arrest and cell apoptosis via CDKs–cyclins and mitochondria‐caspases‐dependent, and PPARγ‐independent signaling pathways in breast cancer cells, without contributions to the cytotoxicity of TAM. J. Cell. Biochem. 113: 2643–2651, 2012. © 2012 Wiley Periodicals, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.24139