Original Article

Growth inhibitory effects and molecular mechanisms of crotoxin treatment in esophageal Eca-109 cells and transplanted tumors in nude mice

Jing-kang He, Xiang-sheng Wu, Yan Wang, Rong Han, Zheng-hong Qin, Yan Xie
DOI: 10.1038/aps.2012.156


Cheng YAO1, 2, 3, Jang-hee OH1, 2, 3, Inn Gyung OH1, 2, 3, Chi-hyun PARK1, 2, 3, *, Jin Ho CHUNG1, 2, 3, *
1Department of Dermatology, Seoul National University College of Medicine, Seoul 110–744, Korea; 2Institute of Dermatological Science, Medical Research Center, Seoul National University, Seoul 110–744, Korea; 3Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 110–744, Korea

Aim: To investigate the effect of [6]-shogaol, an active ingredient in ginger, on melanogenesis and the underlying mechanisms.

Methods: B16F10 mouse melanoma cells were tested. Cell viability was determined with the MTT assay. Melanin content and tyrosinase activity were analyzed with a spectrophotometer. The protein expression of tyrosinase and microphthalmia associated transcription factor (MITF), as well as phosphorylated or total ERK1/2 and Akt were measured using Western blot.

Results: Treatment of the cells with [6]-shogaol (1, 5, 10 µmol/L) reduced the melanin content in a concentration-dependent manner. [6]-Shogaol (5 and 10 µmol/L) significantly decreased the intracellular tyrosinase activity, and markedly suppressed the expression levels of tyrosinase and MITF proteins in the cells. Furthermore, [6]-shogaol (10 µmol/L) activated ERK, which was known to negatively regulate melanin synthesis in these cells. Pretreatment with the specific ERK pathway inhibitor PD98059 (20 µmol/L) greatly attenuated the inhibition of melanin synthesis by [6]-shogaol (10 µmol/L).

Conclusion: The results demonstrate that [6]-shogaol inhibits melanogenesis in B16F10 mouse melanoma cells via activating the ERK pathway.

Keywords: [6]-shogaol; skin pigmentation; melanin; tyrosinase; MITF; ERK; B16F10 mouse melanoma cell

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0008196).
* To whom correspondence should be addressed.
E-mail chppark@hotmail.com (Chi-hyun PARK); jhchung@snu.ac.kr (Jin Ho CHUNG)
Received 2012-04-28 Accepted 2012-08-26

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