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Phytother Res. 2019 Sep 4. doi: 10.1002/ptr.6497. [Epub ahead of print]

Citrus unshiu peel suppress the metastatic potential of murine melanoma B16F10 cells in vitro and in vivo.

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Anti-Aging Research Center, Dong-eui University, Busan, Republic of Korea.
Department of Biochemistry, College of Korean Medicine, Dong-eui University, Busan, Republic of Korea.
Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju, Republic of Korea.
Department of Molecular Biology, College of Natural Sciences, Dong-eui University, Busan, Republic of Korea.
Department of Food and Nutrition, College of Nursing, Healthcare Sciences & Human Ecology, Dong-eui University, Busan, Republic of Korea.
Department of Food and Nutrition, College of Biotechnology & Natural Resource, Chung-Ang University, Anseong, Republic of Korea.
Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea.


The peel of Citrus unshiu Marcow. fruits (CU) has long been used as a traditional medicine that has therapeutic effects against pathogenic diseases, including asthma, vomiting, dyspepsia, blood circulation disorders, and various types of cancer. In this study, we investigated the effect of CU peel on metastatic melanoma, a highly aggressive skin cancer, in B16F10 melanoma cells, and in B16F10 cells inoculated-C57BL/6 mice. Our results show that ethanol extracts of CU (EECU) inhibited cell growth and increased the apoptotic cells in B16F10 cells. EECU also stimulated the induction of mitochondria-mediated intrinsic pathway, with reduced mitochondrial membrane potential and increased generation of intracellular reactive oxygen species. Furthermore, EECU suppressed the migration, invasion, and colony formation of B16F10 cells. In addition, the oral administration of EECU reduced serum lactate dehydrogenase activity without weight loss, hepatotoxicity, nor nephrotoxicity in B16F10 cell-inoculated mice. Moreover, EECU markedly suppressed lung hypertrophy, the number and expression of metastatic tumor nodules, and the expression of inflammatory tumor necrosis factor-alpha in lung tissue. In conclusion, our findings suggest that the inhibitory effect of EECU on the metastasis of melanoma indicates that it may be regarded as a potential therapeutic herbal drug for melanoma.


B16F10 cells; Citrus unshiu (CU); apoptosis; melanoma; metastasis


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