Emodin promotes apoptosis of human endometrial cancer through regulating the MAPK and PI3K/ AKT pathways

Abstract

Emodin, a major component of rhubarb, has anti-tumor effects in a variety of cancers, influencing multiple steps of tumor development through modulating several signaling pathways. The aim of this study is to examine the effect of emodin on cell apoptosis and explore the underlying mechanisms in human endometrial cancer cells. Here we report that emodin can inhibit KLE cell proliferation and induce apoptosis in a time- and dose-dependent manner. Western blot assay found that emodin was involved in MAPK and PI3K/Akt signaling pathways. Specifically, emodin significantly suppressed the phosphorylation of AKT, and enhanced the phosphorylation of MAPK pathways. Furthermore, the generation of reactive oxygen species (ROS) was up-regulated in KLE cells upon treatment with emodin, while the anti-oxidant agent N-acetyl cysteine (NAC) can inhibit emodin-induced apoptosis and promote the activation of AKT and Bcl-2. Taken together, we revealed that emodin may induce apoptosis in KLE cells through regulating the PI3K/AKT and MAPK signaling pathways, indicating the importance of emodin as an anti-tumor agent.

Preclinical Efficacy and Involvement of AKT, mTOR, and ERK Kinases in the Mechanism of Sulforaphane against Endometrial Cancer

“…AKT signaling promotes cell survival by mediating the effects of cellular growth factors, and blocks apoptosis by inactivating pro-apoptotic proteins [53]. Inhibition of AKT phosphorylation has shown promising results in restraining endometrial cell proliferation [54,55]. Based on its role in cancer progression, various inhibitors of PI3K/AKT/mTOR are currently being evaluated in clinical trials for treating patients with metastatic, recurrent, and persistent endometrial cancer.…”

p38β - MAPK11 and its role in female cancers

“…Despite the decreased level of expression, the high level of deep deletion within the gene and differences in methylation may in uence post-transcriptional regulation and phosphorylation of the gene, in uencing its ability to self-activate. For example, therapeutics such as emodin which target phosphorylation are shown to maintain basal levels of genes involved in the p38MAPK pathway while inducting ROS activated apoptosis of cancer cells [47,74] Activation of p38β via the transcription factor Pokemon/Zbtb7 is associated with tumorigenesis and cell invasion in HepG2 cells [30]. Downstream signalling of p38β also leads to an increase in expression of the oncogene, Lipocalin2 (LCN2), and an increase in tumour cell migration [18,30].…”

“…mechanism for future research [47]. Studies have shown that oestradiol is a potential activator of the MAPK pathway through estrogen (ER) and Insulin receptor (InsR) interaction.…”

“…Phosphorylated Akt (p-Akt), mTOR (p-mTOR) and MAPK (p-MAPK) proteins as well as lncRNAs like HEIH, are often implicated in endometrial carcinogenesis and tolerance of common antineoplastic agents such as paclitaxel [50,51]. As such, MAPK and PI3K/Akt are promising targets of new anti-tumor agents such as emodin (rhubarb) [47].…”

The Health Benefits of Emodin, a Natural Anthraquinone Derived from Rhubarb—A Summary Update

“…The effect of emodin on cell proliferation was studied and confirmed for many cancer cell lines, including breast [40], skin [41], pancreas [42], colon [43,44], ovarian [45], prostate [46], esophageal [47], bladder [48], and endometrial [49]. For example, the IC50 values for MCF-7 (breast) and HepG2 (liver) cancer cells were 52.72 μM and 43.87 μM, respectively [50].…”