Chemopreventive and chemosensitizing effects of clove oil and its main components in melanoma cells

Background. Clove oil is an essential oil obtained by steam or water distillation of the buds, leaves or stems of Syzygium aromaticum (L) Merr. & Perry. (Fam. Myrtaceae). It has been used traditionally to relief skin ailments such as burns, wounds and scars [1], owing to its antimicrobial, antioxidant and anti-inflammatory properties [1-3]. Moreover, it has been reported to possess anticancer properties in different cancer cell models, likely inducing cell cycle arrest or apoptosis, oxidative stress, cytotoxicity and antimetastatic effects [1]. In line with this evidence, in the present study we investigated the potential antiproliferative and chemosensitizing properties of a clove essential oil in melanoma in vitro models. Cutaneous melanoma is an aggressive solid tumor, with an increasing incidence every year, despite limited or ineffective targeted therapeutic options [4]. Therefore, studying novel therapeutic opportunity and highlighting possible strategies to counteract chemoresistance thus restoring the chemotherapy efficacy are considered emerging objectives [3]. Methodologies. A sample of clove essential oil (provided by SoriaNatural, Spain) was assayed for its anticancer activity and chemosensitizing effects in combination with the anticancer drugs doxorubicin and sorafenib in different human malignant melanoma cell lines, including A375 and M14, derived from the skin and metastatic sites, respectively. Moreover, the contribution of the main compounds of the clove essential oil, as revealed at gas-chromatographic analysis, was evaluated too. The ability of the tested samples to affect cell viability both alone and in combination with anticancer drugs was determined by the MTT assay; moreover, the lactate dehydrogenase release, the intracellular levels of reactive oxygen species and the cell migration abilities were measured as previously reported [5]. Results. The obtained results highlighted that clove essential oil progressively inhibited the cancer cell proliferation, likely inducing intracellular oxidative stress and lactate dehydrogenase release. Among the phytochemicals identified at gas-chromatographic analysis, eugenol mainly contributed to the cytotoxicity activity of the clove oil, although its effects were found increased by the presence of caryophyllane sesquiterpenes. Accordingly, the essential oil induced a marked inhibition of the melanoma cell migration, which was ascribed to the combined activities of eugenol and caryophyllane sesquiterpenes. At last, clove oil potentiates the anticancer activity of known chemotherapeutic drugs, especially sorafenib, thus suggesting the modulation of possible mechanisms involved in cancer chemoresistance. Conclusions. Present findings encourage further studies to clarify the mechanisms underlying the anticancer activity of clove oil in melanoma and to underpin its future application in the pharmaceutical field. References [1] Batiha et al. Biomolecules 2020,10,202. [2] Rahmasari et al. Medicine 2022,2,141-148. [3] Alexa et al. Molecules 2022,27,990. [4] Villani et al. Int J Mol Sci 2022,23,6388. [5] Di Sotto et al. Biomedicines 2022,10,2257.