Wedelolactone, a Component from Eclipta prostrata (L.) L., Inhibits the Proliferation and Migration of Head and Neck Squamous Cancer Cells through the AhR Pathway

Abstract

Background: Ecliptae prostrata (L.) L. has been widely used in east Asia with reported biological activities including anti-cancer properties. Objective: We aimed to investigate the effect of ethyl acetate extract of Ecliptae prostrata (L.) L. (EAE) and its component wedelolactone on the proliferation and migration of head and neck squamous cancer cells. Methods: The proliferation of human SCC-4 and mouse CU110-1 tongue squamous carcinoma cells was assessed using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method. Scratch wound assays were performed to assesse cell migration rates. The levels of E-cadherin and vimentin were used as markers of the epithelial-to-mesenchymal transition (EMT). AhR, CYP1A1 and CYP1B1 levels were examined to uncover the mechanism of inhibition of cell migration by wedelolactone. Results: We found that EAE and wedelolactone decreased the proliferation of human SCC-4 cells and mouse CU110-1 cells at doses of EAE at > 25 μg/ml and wedelolactone at > 6.25 μg/ml. Similarly, both EAE and wedelolactone produced inhibitory effects against migration but the effective doses that significantly inhibited migration were lower than those affecting proliferation. Wedelolactone below 12.5 μg/ml inhibited the epithelial-to-mesenchymal transition (EMT) with increased expression of E-cadherin and decreased expression of vimentin in SCC-4 and CU110-1 cells. Further analysis showed wedelolactone inhibited the expression of AhR and its downstream target molecules CYP1A1 and CYP1B1 in both squamous carcinoma cells at the same doses inhibiting cell migration. Addition of benzo (a)pyrene [B(a)P], an agonist of AhR, stimulated migration, especially in the CU110-1 cells with reported cancer stem cell-

Recent advances in the potential effects of natural products from traditional Chinese medicine against respiratory diseases targeting ferroptosis

“…Research demonstrated that OB significantly mitigated lung histopathological injury, reduced the release of inflammatory cytokines, and decreased levels of Fe 2+ and 4-HNE, by inhibiting Nrf2 ubiquitination and upregulating the Nrf2/SLC7A11/GPX4 signaling pathway, ↑: up-regulation, increase or activation; ↓: down-regulation, decrease or inhibition ultimately inhibiting iron-dependent ferroptosis and alleviating LPS-induced ALI [131]. Wedelolactone (Wed) is the principal active component of Eclipta prostrata and is categorized as a lactone [132]. Research findings indicate that Wed mitigates pancreatitis and associated lung damage in mouse models induced by taurine cholate or small proteins.…”

Network pharmacology-based strategy for predicting therapy targets of Ecliptae Herba on breast cancer

“…Studies have shown that multiple components of Ecliptae Herba have anti-tumor activities. [10][11][12][13] Yadav explored the inhibitory effects of Ecliptae Herba ethanol extract on 7 different cancer cell lines and found that the proliferation and migration of breast cancer cells were the most inhibited. [14] However, the mechanism of action of Ecliptae Herba in breast cancer treatment remains unknown.…”