α-terpineol induces apoptosis in melanoma cells and its underlying mechanism

Cutaneous melanoma is an aggressive skin Cancer known for its ability to metastasize, resist treatment, and result in poor outcomes. With rising global incidence, early diagnosis and effective treatment strategies are imperative. Plant-derived extracts and natural compounds have emerged as promising therapeutic agents against various cancers, including melanoma. α-Terpineol, a volatile monoterpenoid alcohol found in pine needle oil and Other essential oils, has demonstrated significant antitumor activity. We evaluated α-terpineol’s effects using scratch wound, Transwell, and colony formation assays to assess migration, invasion, and clonogenicity. Cell proliferation and Apoptosis were examined via EdU and AO/EB staining, while flow cytometry analyzed cell cycle distribution and Apoptosis rates. Potential targets were identified through network pharmacology and molecular docking, while Western blotting confirmed pathways related to Apoptosis. A B16-F10 xenograft model was used to further validate in vivo efficacy. In vitro studies demonstrated that α-terpineol inhibits melanoma cell proliferation, migration, and invasion by triggering Apoptosis. Network pharmacology identified the JAK2/STAT3 signaling pathway as crucial, with Western blot analysis showing reduced levels of p-JAK2 and p-STAT3. In vivo, α-terpineol inhibited tumor growth without causing systemic toxicity. α-Terpineol may attenuate melanoma progression by inhibiting JAK2/STAT3 signaling, highlighting its potential as a novel therapeutic candidate.

Supplementary Information: The online version contains supplementary material available at 10.1038/s41598-025-34538-7.

Cell proliferation; Cutaneous melanoma; JAK2/STAT3 signaling pathway; Pine needle oil; α-terpineol.