Present address: School of Bio Sciences and Technology, VIT University, Vellore 632014, Tamil Nadu, India.
Exploration of effects of emodin in selected cancer cell lines: enhanced growth inhibition by ascorbic acid and regulation of LRP1 and AR under hypoxia-like conditions
Article first published online: 5 DEC 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 34, Issue 1, pages 95–104, January 2014
How to Cite
Masaldan, S. and Iyer, V. V. (2014), Exploration of effects of emodin in selected cancer cell lines: enhanced growth inhibition by ascorbic acid and regulation of LRP1 and AR under hypoxia-like conditions. J. Appl. Toxicol., 34: 95–104. doi: 10.1002/jat.2838
- Issue published online: 29 OCT 2013
- Article first published online: 5 DEC 2012
- Manuscript Accepted: 3 OCT 2012
- Manuscript Revised: 22 SEP 2012
- Manuscript Received: 26 MAY 2012
- prostate cancer;
- ascorbic acid;
- LDL receptor-related protein 1;
- androgen receptor;
- reactive oxygen species
This study explores the link between the antiproliferative activity of emodin through the generation of reactive oxygen species (ROS) in various cancer cell lines and the expression of the androgen receptor (AR) in the prostate cancer cell lines LNCaP (androgen-sensitive) and PC-3 (androgen-refractory), as well as the pro-metastatic low-density lipoprotein receptor-related protein 1 (LRP1) in the above prostate cancer cells and the nonprostate cell lines A549 (lung), HCT-15 (colon) and MG-63 (bone) under normoxic and hypoxia-like conditions. Among all cell lines, emodin showed most growth inhibition in LNCaP, followed by A549. The mechanism of cytotoxicity of emodin was postulated to be the widely reported ROS generation, based on the observations of poor in vitro radical-scavenging activity and increased growth inhibition of emodin by ascorbic acid (AA) pre-treatment owing to the additive effects of ROS generation by emodin and pro-oxidant effects of AA. Emodin downregulated AR in LNCaP under normoxic and hypoxia-like conditions (simulated by CoCl2) and LRP1 under normoxia. Emodin upregulated LRP1 in other cell lines, except HCT-15, under normoxic, and even more markedly under hypoxia-like conditions. The downregulation of AR in LNCaP and upregulation of LRP1 in all cell lines, except HCT-15, under hypoxia-like conditions along with growth inhibition by emodin, suggests that emodin may be a useful therapeutic option against androgen-sensitive prostate cancer and other such LRP1-expressing cancers to attempt the targeting of the elevated LRP1 levels to allow the uptake of emodin and/or any other accompanying therapeutic agents by LRP1. Copyright © 2012 John Wiley & Sons, Ltd.