Arctigenin inhibits human breast cancer cell proliferation, migratory and invasive abilities and epithelial to mesenchymal transition by targeting 4EBP1

Abstract

Breast cancer (BC) is one of the most common types of cancer with the highest morbidity rate amongst all cancers in women worldwide. Arctigenin is isolated from the seeds of Asteraceae lappa and exhibits anti-inflammatory and anti-viral effects. The present study aimed to investigate the effect of arctigenin on BC cells and to explore the regulation of arctigenin on eukaryotic translation initiation factor 4E binding protein 1 (4EBP1) expression. To do so, MDA-MB-231 and BT549 cells were treated with arctigenin at various concentrations (0, 5, 10, 20 and 40 µM). Cells treated with 40 µM arctigenin were transfected with pcDNA3.1-4EBP1 or NC control. Cell Counting Kit-8 assay was used to determine cell proliferation, reverse transcription quantitative PCR was used to evaluate the transfection efficiency, western blotting was used to detect relative protein expression and Transwell assays were performed to evaluate the migratory and invasive abilities of BC cells. The results demonstrated that arctigenin could inhibit the proliferation, migratory and invasive abilities, and epithelial to mesenchymal transition (EMT) of MDA-MB-231 and BT549 cells. Furthermore, arctigenin downregulated the expression of 4EBP1 in MDA-MB-231 and BT549 cells, whereas 4EBP1 overexpression could reverse the inhibiting effect of arctigenin on proliferation, migratory and invasive abilities, and EMT in MDA-MB-231 and BT549 cells. The findings suggested that arctigenin may inhibit human BC cell proliferation, migratory and invasive abilities, and EMT by targeting 4EBP1.

Tailoring Potential Natural Compounds for the Treatment of Luminal Breast Cancer

“…Arctigenin (18), a bioactive compound from Arctium lappa L., also binds to ERs and reduces pro-tumor signals, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), MMP-3, MMP-9, and thymic stromal lymphopoietin (TSLP). In addition, it inhibits the proliferation and invasion of luminal BC cells [233,[324][325][326].…”

Targeting PI3K/Akt signaling in prostate cancer therapy

“…Silencing circ‐0030586 suppresses growth and invasion of prostate tumor cells. Circ‐0030586 stimulates PI3K/Akt signaling to induce EMT in increasing progression and invasion of prostate tumor cells (Luo et al 2021a, b, c). Since Akt induction promotes prostate cancer metastasis, its inhibition can pave the way for reducing tumor progression.…”

“…This compound stimulates apoptosis and decreases viability of tumor cells. It affects various molecular pathways such as STAT3 and β‐catenin in impairing tumor progression (Shi et al 2020; Sun et al 2018a, b; Janthamala et al 2021; Luo et al 2021a, b, c). Acidic tumor microenvironment induces drug resistance in prostate cancer.…”

Targeted Delivery of Arctigenin Using Sialic Acid Conjugate-Modified Liposomes for the Treatment of Breast Cancer

“…Arctigenin (ATG) ( Figure 1 ) is a phenylpropanoid dibenzyl butyrolactone lignan compound, one of the primary bioactive ingredients from the medicinal plant Arctium lappa L. ATG possesses notable pharmacological activity, such as anti-inflammatory [ 1 , 2 ], immunoregulatory, antiviral, PP2A activation [ 3 ], and anticancer activities [ 4 , 5 ]. Many studies in the literature show that ATG is a broad-spectrum antitumor drug with an excellent inhibitory effect on malignant tumors such as breast cancer [ 6 , 7 ], glioblastoma [ 8 ], liver cancer [ 9 , 10 ], and colon cancer [ 11 , 12 , 13 ]. The molecular mechanisms behind ATG’s biological effects have been intensively studied [ 4 , 13 , 14 ].…”

“…The molecular mechanisms behind ATG’s biological effects have been intensively studied [ 4 , 13 , 14 ]. The anticancer mechanisms include cytotoxicity [ 15 ], suppression of proliferation [ 16 ], induction of apoptosis [ 17 ], repression of angiogenesis, migration and invasion of cancer cells [ 7 ], enhancement of drug cytotoxicity [ 18 ], and immunomodulatory effects [ 19 ]. ATG regulates the immune system as an immunomodulator through its anti-inflammatory effect, thus exerting an antitumor effect.…”