Therapeutic Potential of 2-Cyclopenten-1-one in Malignant Melanoma Through Combined Cytotoxic and Anti-inflammatory Actions

Melanoma is one of the most aggressive types of skin cancer, with its increasing incidence being linked to elevated exposure to ultraviolet (UV) radiation. Due to the limited efficacy of current therapies, there is a need to explore novel natural therapeutic agents. This study investigated the biological effects of 2-cyclopenten-1-one (2-CP), a naturally occurring compound found in Arum dioscoridis, were investigated on the human melanoma cell line (SK-MEL-30) and the healthy fibroblast cell line (L929). The cytotoxic and antiproliferative properties of the compound were evaluated using MTT and colony formation assays. Changes in the expression of TGF-β protein were analysed using Western blot. The findings revealed that 2-cyclopenten-1-one had a dose-dependent cytotoxic effect, demonstrating approximately 3-fold the toxicity of melanoma cells compared to healthy fibroblasts. (IC₅₀: SK-MEL-30, 58.8 µM; L929, 156.6 µM). Furthermore, the compound reduced colony formation by 76% and completely suppressed proliferation at a concentration of 100 µM. Western blot analysis revealed that LPS treatment increased TGF-β expression by approximately 1.5-fold. In contrast, 2-cyclopenten-1-one reduced this increase, restoring expression levels to near-baseline levels. These results suggest that the compound may have anti-tumour effects by inhibiting TGF-β-mediated proliferative signalling pathways. In conclusion, 2-cyclopenten-1-one emerges as a potential natural therapeutic agent with selective cytotoxicity against melanoma cells and a low toxicity profile. Further in vitro and in vivo investigations are needed to elucidate the compound’s anticancer and immunomodulatory mechanisms.