Cutaneous melanoma (CM) is an aggressive and difficult-to-treat skin cancer subtype that originates from malignant mutations in melanocytes. It can spread to other organs in a process called metastasis [1]. The incidence of melanoma continues to increase worldwide and deserves attention. In 2020, were diagnosed 324.635 cases and 57.043 deaths from CM. Predictions indicate that by 2040 there will be an increase of more than 50% in the number of cases of this disease [2,3]. This pathology is linked to excessive or unprotected sunbathing, which leads to mutations in DNA by ultraviolet (UV) radiation [4].

Nowadays, cancer immunotherapies, such as checkpoint inhibitors ipilimumab, nivolumab and pembrolizumab, are routinely used as adjuvant and neoadjuvant treatments in melanoma patients, and have improved previously poor survival. In general, these immunotherapies act on programmed cell death protein-1 (PDL-1) and cytotoxic T lymphocyte antigen-4 (CTL-4), which are proteins involved tumour immune evasion [5,6]. However, the use of this therapeutic strategy is associated with severe side effects and poor quality of life. Moreover, there is a risk of resistance immediately after treatment for several months [7]. Thus, there is an urgent need for new drugs or adjuvant therapies to improve patient survival and health quality [8].

In this context, the potential of phenolic compounds to be used in cancer as therapeutic adjuvants have been highlighted in recent years, and RA, a phenolic acid, has been indicated to treat CM [9]. Several studies have shown that RA exhibits anticancer effects, such as in breast cancer [10], prostate cancer [11], and hepatocellular carcinoma [12]. In addition to these anticancer effects, it seems to be an antioxidant compound [13]. With this, more research should be carried out to clearly elucidate the possibilities regarding cell signalling pathways in which the RA may exert a pharmacological action against cancer.

Therefore, in this study, we aimed to explore the effects of the phenolic compound RA on the human metastatic melanoma cell line SK-MEL-28. We assessed the potential of RA to affect the viability and migration of cells, oxidative stress and antioxidant markers, and searched for a plausible cell signalling pathway to explain the observed cell death. We hypothesised that the mechanisms of apoptosis and the inhibition of cell migration might be due to the ability of RA to alter the expression of some apoptotic genes and enzymatic apoptotic effectors.