Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

Abstract

Malignant melanoma (melanoma malignum) is one of the most dangerous types of tumor. It is very difficult to cure. In recent years, a lot of attention has been given to chemoprevention. This method uses natural and synthetic compounds to interfere with and inhibit the process of carcinogenesis. In this study, a new treatment strategy was proposed consisting of a combination of 5,7-dimethoxycoumarin (DMC), an activator of melanogenesis, and valproic acid (VPA), a well-known drug that is one of the histone deacetylase inhibitors (HDACis). In conjunction with 1 mM VPA, all of the tested concentrations of DMC (10–150 μM) significantly decreased the proliferation of A-375 cells. VPA and DMC also induced the synthesis of melanin and the formation of dendrite and star-shaped cells. Tyrosinase gene expression and tyrosinase activity significantly increased in response to VPA treatment. Pyrolysis with gas chromatography and mass spectrometry (Py-GC/MS) was used to investigate the structure of the isolated melanin. This showed that the quantitative and qualitative components of melanin degradation products are dependent on the type of applied melanogenesis inductor. Products derived from eumelanin were detected in the pyrolytic profile of melanin isolated from A-375 cells stimulated with DMC. Thermal degradation of melanin isolated from melanoma cells after exposure to VPA or a mixture of VPA and DMC revealed the additional presence of products derived from pheomelanin.

Discovery of new depigmenting compounds and their efficacy to treat hyperpigmentation: Evidence from in vitro study

“…The Dermal Irritection® test method is based on measurable changes in biological macromolecules that involves protein denaturation and disaggregation after exposure to skin depigmenting compounds. Similar results of irritancy test of some bioactive compounds using human and Dermal Irritection® test methods have been reported elsewhere …”

Effects of gamma-irradiated soybean pod extract on oxidative stress, cancer cell viability, and tyrosinase inhibition

“…Tyrosinase synthesizes skin pigments and the browning of fruits and vegetables (Ramsden & Riley, ). However, overproduction of melanin can lead to the development of malignant melanoma, a cancer with a rapidly increasing incidence (Chodurek et al, ). Tyrosinase activity is influenced by the hydroxyl groups of phenolic compounds by virtue of the formation of hydrogen bonds with the enzyme active site; this causes steric hindrance or structural modifications (Alam, Yoon, Lee, Cho, & Lee, ).…”

Upregulation of Melanogenesis and Tyrosinase Activity: Potential Agents for Vitiligo

“…Chodurek et al [ 90 ] reported a new treament for malignant melanoma consisting of a combination of valproic acid (VPA) and 5,7-dimethoxycoumarin (DMC) ( Figure 20 ). In A375 cells, the results demonstrated that both compunds could enhance the synthesis of melaninand the formation of dendrite and star-shaped cells.…”