Ellagic acid induces cell cycle arrest and apoptosis via the TGF‑β1/Smad3 signaling pathway in human colon cancer HCT‑116 cells

Abstract

Colorectal carcinoma (CRC) is a major type of malignancy worldwide. Ellagic acid (EA), a natural phenolic constituent, has been shown to exhibit anticancer effects. In our previous study, it was shown that EA inhibited proliferation of CRC cells. Additionally, microarray analysis revealed 4,738 differentially expressed genes (DEGs) which were associated with multiple cellular events, including cell growth, apoptosis and angiogenesis. However, the associated pathways had not been validated. In the present study, it was shown that EA induced G0/G1 cell cycle arrest in HCT-116 cells, and increased apoptosis. Furthermore, DEGs identified by cDNA microarray analysis were investigated, and showed changes in five genes which were associated with the TGF-β1/Smad3 signaling pathway. TGF-β1 small interfering RNA and SIS3, a Smad3 inhibitor, were used to assess the role of TGF-β1 and Smad3, respectively, and it was shown that the they reduced the effects of EA on HCT-116 CRC cells. In addition, the expression patterns of downstream DEGs of the TGF-β1/Smad3 pathway were altered. Thus, this pathway may underlie the molecular mechanism by which EA exhibits its effects in vitro in CRC cells. Accordingly, targeting the TGF-β1/Smad3 pathway with anticancer agents such as EA may be potentially used to treat CRC.

Combined Methylome and Transcriptome Analyses Reveals Potential Therapeutic Targets for EGFR Wild Type Lung Cancers with Low PD-L1 Expression

“…In the present study, it was identified to be hypermethylated in gene body but was related with up-regulated gene expression. Of the 6 drugs targeting CA9, benzthiazide [ 43 ], hydroflumethiazide [ 44 ], WX-G250 [ 45 ], and ellagic acid [ 46 ] have shown antitumor properties. SLC7A11 encodes the light chain subunit of cystine/glutamate antiporter system xc—and is involved in glutamine metabolism.…”

Ferroportin-dependent ferroptosis induced by ellagic acid retards liver fibrosis by impairing the SNARE complexes formation

“…Moreover, immunofluorescence costaining verified that α-SMA-positive cells undergo ferroptotic processes. A study revealed that EA can inhibit colon cancer and esophageal cancer development by inducing cell cycle arrest and apoptosis [ 41 , 42 ]. In our studies, the ferroptosis inhibitor ferrostatin-1 relieved the growth inhibition of HSCs induced by EA, while ZVAD-FMK (an apoptosis inhibitor) could not.…”

A Bioactive Compound from Sanguisorba officinalis L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells

“…Ellagic acid (EA), a natural phenolic constituent, has been shown to exhibit anti-cancer effects. Zhao studied EA targeted to the TGFbeta1/Smad3 pathway on HCT116 cells, which might be potentially used to treat CRC [27]. Additionally, they also found that EA modified a large number of cellular functions, including proliferation, apoptosis, cell cycle, and angiogenesis [28].…”