Isoliquiritigenin-Induced Differentiation in Mouse Melanoma B16F0 Cell Line

Abstract

The chemotherapeutical treatment is very limited for malignant melanoma, a highly lethal disease occurs globally. Natural products derived from traditional Chinese medicine licorice are attractive in quest new treatments due to their anti-tumor activities. A new dietary flavonoid isoliquiritigenin (ISL) were thus investigated to indentify its anti-melanoma activities on mouse melanoma B16F0 cells in present study. Using biochemical and free radical biological experiments in vitro, we identified the pro-differentiated profiles of ISL and evaluated the role of reactive oxygen species (ROS) during B16F0 cell differentiation. The data showed a strong dose-response relationship between ISL exposure and the characteristics of B16F0 differentiation in terms of morphology changes and melanogenesis. The accumulated intercellular ROS during exposure are necessary to support ISL-induced differentiation, which was proven by additional redox modulators. It was confirmed further by the relative activities of enzymes and genes modulated melanogenesis in ISL-treatments with or without ROS modulators. The tumorigenicity of ISL-treated cells was limited significantly by using the colony formation assay in vitro and an animal model assay in vivo respectively. Our research demonstrated that isoliquiritigenin is a differentiation-inducing agent, and its mechanisms involve ROS accumulation facilitating melanogenesis.

Licochalcone A inhibiting proliferation of bladder cancer T24 cells by inducing reactive oxygen species production

“…A growing body of evidence indicates that ROS play an important role in inhibiting cancer cells proliferation through inducing apoptosis and differentiation [20,21]. For example, GSH depletion induced by BSO decreased proliferation of HL60 cells and promoted cell differentiation [22].…”

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis

“…The dopachrome levels were determined at 492 nm [69]. TYRP1 expression was assessed by western blot using anti-TYRP1 antibody (Abcam) and β-actin antibody (Sigma) as loading control.…”

A Review: The Pharmacology of Isoliquiritigenin

“…The results demonstrated that ISL exerted higher cytotoxicity against the all tumor cell lines than normal cells, with the ability to induce internucleosomal DNA fragmentation and activate caspase‐3, caspase‐8, and, caspase‐9 dose dependently in HL‐60 cells (Chowdhury et al , ). The study of Chen et al (2013) (Chen et al , 2013) showed that the exposure of ISL could facilitate differentiation in HL‐60 cells, which resulted in ameliorating morphology changes. Isoliquiritigenin also decreased iROS‐reduced nitro blue tetrazolium chloride activities and expression levels of surface antigens CD11b/CD14 through modulation of the nuclear erythroid‐related factor 2/antioxidant responsive element [NF‐E2‐related factor 2 (Nrf2)/ARE (antioxidant responsive element)] pathway.…”

“…As for in vivo assay , ISL pretreatment inhibited the tumor of B16F0 cells. The mechanism was involving the increase of iROS formation and accumulation facilitating melanogenesis (Chen et al , ). Additionally, ISL significantly inhibited A549 human lung cancer cell line proliferation by restraining the cell cycle progression at G1 and G2/M phase, meanwhile, enhancing the expression of p53 and p21 CIP1/WAF1 , improving Fas and its two ligands (Hsu et al , ) (Ii et al , ).…”