Antiproliferative and Proapoptotic Effects of Erucin, a Diet-Derived H2S Donor, on Human Melanoma Cells

Abstract

Melanoma is the most dangerous form of skin cancer and is characterized by chemotherapy resistance and recurrence despite the new promising therapeutic approaches. In the last years, erucin (ERU), the major isothiocyanate present in Eruca sativa, commonly known as rocket salads, has demonstrated great efficacy as an anticancer agent in different in vitro and in vivo models. More recently, the chemopreventive effects of ERU have been associated with its property of being a H2S donor in human pancreatic adenocarcinoma. Here, we investigated the effects of ERU in modulating proliferation and inducing human melanoma cell death by using multiple in vitro approaches. ERU significantly reduced the proliferation of different human melanoma cell lines. A flow cytometry analysis with annexin V/PI demonstrated that ERU was able to induce apoptosis and cell cycle arrest in A375 melanoma cells. The proapoptotic effect of ERU was associated with the modulation of the epithelial-to-mesenchymal transition (EMT)-related cadherins and transcription factors. Moreover, ERU thwarted the migration, invasiveness and clonogenic abilities of A375 melanoma cells. These effects were associated with melanogenesis impairment and mitochondrial fitness modulation. Therefore, we demonstrated that ERU plays an important role in inhibiting the progression of melanoma and could represent a novel add-on therapy for the treatment of human melanoma.

Ircinia ramosa Sponge Extract (iSP) Induces Apoptosis in Human Melanoma Cells and Inhibits Melanoma Cell Migration and Invasiveness

“…E-Cadherin (E-CAD) and N-Cadherin (N-CAD) expression levels were evaluated in iSP-treated A375 (1 µg/mL for 48 h) via extracellular staining with APC-Cy7 antihuman CD324 (E-CAD) (67A4, Biolegend, 1:50) and FITC antihuman CD325 (N-CAD) (8C11, Biolegend, 1:50) as previously reported [56].…”

Erucin, an H2S-Releasing Isothiocyanate, Exerts Anticancer Effects in Human Triple-Negative Breast Cancer Cells Triggering Autophagy-Dependent Apoptotic Cell Death

“…Among them, erucin (4-methylthiobutyl isothiocyanate) is one of the major components of leaves obtained from the enzymatic hydrolysis of glucoerucin. As demonstrated in a large number of in vitro and in vivo studies, erucin exerts protective effects against several types of human cancers, including breast cancer [ 8 , 11 , 12 , 13 , 14 , 15 ]. Remarkably, recent findings revealed that the protective effect of erucin relies on its intrinsic capacity to slowly release hydrogen sulfide (H 2 S), which is one of three gasotransmitters, along with nitric oxide (NO) and carbon monoxide (CO), which act in our body to modulate numerous biological processes [ 16 ].…”

Reactive Sulfur Species in Biology and Medicine

“…H 2 S-releasing compounds have also emerged as potential therapeutics for various types of cancers. Ianaro, Ercolano, and co-workers examine the effects of erucin (ERU), a compound derived from the dietary source, on human melanoma cell lines [ 4 ]. ERU was found to exert a significant inhibitory effect on human melanoma cell lines.…”