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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Transcriptome Analysis of Linalool-Induced Hypopigmentation in B16 Melanoma Cells

  1. 1Faculty of Science and Technology, Sophia University, Chiyoda City 102-8554, Tokyo, Japan
  2. 2Institute of Life and Environmental Science, University of Tsukuba, Tsukuba City 305-8572, Ibaraki, Japan
  3. 3Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba City 305-8572, Ibaraki, Japan

Abstract

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.

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BibTeX
@article{villareal2026transcriptome,
  title = {{Transcriptome Analysis of Linalool-Induced Hypopigmentation in B16 Melanoma Cells}},
  author = {Myra O. Villareal and Hiroko Isoda},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27208956},
  url = {https://www.mdpi.com/1422-0067/27/20/8956},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Transcriptome Analysis of Linalool-Induced Hypopigmentation in B16 Melanoma Cells
AU  - Myra O. Villareal
AU  - Hiroko Isoda
PY  - 2026
DA  - 2026/10/09
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27208956
UR  - https://www.mdpi.com/1422-0067/27/20/8956
AB  - 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.
SN  - 1422-0067
ER  -