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

Abstract

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 CoCl(2)) 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.

Emodin: One Main Ingredient of Shufeng Jiedu Capsule Reverses Chemoresistance of Lung Cancer Cells Through Inhibition of EMT

“…Among many natural extracts, Emodin is one of compounds which is recognized as a drug candidate for cancer therapy. Previous reports have shown that Emodin inhibits cell growth in several types of cancer cells by regulating genes related to apoptosis, oncogenesis, proliferation and cancer cell invasion and metastasis [16, 17]. In this study, we examined Emodin and Dox effects to lung cancer.…”

“…Emodin induces cell cycle arrest and apoptosis in cancer cells. According to previous reports [6, 7], Emodin has been proved to have good effects in preventing tumors, however, the effects and mechanism of Emodin on the chemoresistance have not reported.…”

Traditional usages, botany, phytochemistry, pharmacology and toxicology of Polygonum multiflorum Thunb.: A review

“…Emodin has also been found to exhibit cytotoxic effects against HepG2 cells (Yu, et al, 2013), the prostate cancer cell lines LNCaP and PC-3, the lung cancer cell line A549, the colon cancer cell line HCT-15, the bone cancer cell line MG-63 (Masaldan and Iyer, 2014) and the esophageal cancer cell lines EC-109 .…”

Targeted abrogation of diverse signal transduction cascades by emodin for the treatment of inflammatory disorders and cancer

“…Furthermore, emodin decreased the association of AR and heat shock protein 90 and increased the association of AR and MDM2, which in turn induced AR degradation through proteasome-mediated pathway in a ligand-independent manner [60]. Emodin down-regulated AR in LNCaP under normoxic and hypoxia-like conditions (simulated by CoCl 2 and low-density lipoprotein receptor-related protein 1 (LRP1) under normoxia [61]. Similarly, Yu et al [43] showed that in LNCaP cells emodin reduces the expression and function of AR and enhances the expression of p53 and p21.…”