The therapeutic potential and molecular mechanism of Alpha-pinene, Gamma-terpinene, and P-cymene against melanoma cells

The purpose of this study is to investigate the potential anticarcinogenic effects of three phytochemicals, namely <i>Alpha-pinene</i> (AP), <i>Gamma-terpinene</i> (GT), and <i>P-cymene</i> (PC), on melanoma cells (A2058 cell line). Additionally, the study aims to explore the synergistic activities of these phytochemicals with Dacarbazine, a chemotherapy drug. To understand the molecular mechanism involved in apoptosis induction in the A-2058 cell line, it was used AO/EB staining for apoptosis detection and cell cycle analysis, monitored through flow cytometry. It also determined the mRNA expression levels of different apoptosis-regulatory genes, including <i>p53, Bax, NF-kB, Bcl-2, Bcl-xl</i>, and caspase-3. The antitumor activities of these phytochemicals and their combinations were investigated in a subcutaneous mouse tumor model. The tumor diameter was 21.4 ± 1.1 mm in the Dacarbazine treatment group and 42.4 ± 3.1 mm in the control group. The antitumoral activities of AP and PC in the tumor model were similar to those of Dacarbazine. On the other hand, GT exhibited remarkable antitumoral activity, with a 1.75-fold reduction in tumor diameter compared to the Dacarbazine group. When different combinations of phytochemicals and Dacarbazine were used, the GT plus Dacarbazine treatment group was found to have a 3.5-fold reduction in tumor diameter compared to the Dacarbazine group. The tumor diameters in the Dacarbazine, AP plus GT, GT plus Dacarbazine, and AP plus Dacarbazine treatment groups were 21.4 ± 1.1, 7.6 ± 2.2, 8.6 ± 0.5, and 6.2 ± 1.9 mm, respectively.