Transcriptome Analysis of Linalool-Induced Hypopigmentation in B16 Melanoma Cells

Plant-derived phytochemicals exhibit significant pharmacological potential in chronic diseases, including melanoma. Since hyperactive melanogenesis is closely linked to melanoma progression, targeting this pathway with natural bioactive agents represents a major therapeutic strategy. The plant-derived terpene linalool induces cancer-specific oxidative stress in colon cancer cells, as we have previously reported. Here, we characterized the effects of linalool on B16-F10 melanoma cells to establish a transcriptomic baseline of hypopigmentation networks using phenotypic assays and high-throughput RNA-seq profiling. Non-toxic doses of linalool significantly inhibited melanin synthesis, accompanied by a marked reduction in tyrosinase protein abundance. RNA-seq identified 31 significantly upregulated and 48 significantly downregulated genes (p < 0.05), with PCA and cluster analysis demonstrating a distinct transcriptomic profile. Functional GO enrichment revealed candidate regulatory networks involving lysosomal components, the neurofilament cytoskeleton, and cell-cycle checkpoints. While core melanogenesis transcripts (Mitf, Tyr, Dct) showed only minor, non-significant variations, key stress-adaptation and cell-plasticity regulators (Mir210, Dll1) were significantly suppressed. This profile indicates a state of latent molecular vulnerability, mirroring the oxidative responses in colon cancer cells. Taken together, these findings provide a foundational transcriptomic repository of linalool-responsive networks, uncovering critical candidate pathways that modulate melanin production and antioxidant defenses to guide future functional validation and therapeutic exploration of botanical bioactives in melanoma research.