4-(Phenylsulfanyl)butan-2-One Suppresses Melanin Synthesis and Melanosome Maturation In Vitro and In Vivo.
In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanyl)butan-2-one could successfully inhibit pigment generation processes in mushroom tyrosinase platform assay, probably through the suppression of tyrosinase activity to be a non-competitive inhibitor of tyrosinase. In cell-based viability examinations, it demonstrated low cytotoxicity on melanoma cells and other normal human cells. It exhibited stronger inhibitions of melanin production and tyrosinase activity than arbutin or 1-phenyl-2-thiourea (PTU). Also, we discovered that 4-(phenylsulfanyl)butan-2-one reduces the protein expressions of melanin synthesis-related proteins, including the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (Trp-1), dopachrome tautomerase (DCT, Trp-2), and glycoprotein 100 (GP100). In an in vivo zebrafish model, it presented a remarkable suppression in melanogenesis after 48 h. In summary, our in vitro and in vivo biological assays showed that 4-(phenylsulfanyl)butan-2-one possesses anti-melanogenic properties that are significant in medical cosmetology.
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804, Taiwan, ROC. sunbear@cm1.hinet.net.
Shing-Yi Sean
SY
Wu
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804, Taiwan, ROC. davidw@kmu.edu.tw.|Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. davidw@kmu.edu.tw.|Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. davidw@kmu.edu.tw.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. davidw@kmu.edu.tw.
Hui-Min David
HM
Wang
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804, Taiwan, ROC. weneasa@gmail.com.
Yi-Shan
YS
Wen
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. liuwangta@kmu.edu.tw.|Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. liuwangta@kmu.edu.tw.
Wangta
W
Liu
Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. s27159@gmail.com.
Pin-Hui
PH
Li
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. cchiu@kmu.edu.tw.|Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan, ROC. cchiu@kmu.edu.tw.|Translational Research Center, Cancer Center, Department of Medical Research, and Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. cchiu@kmu.edu.tw.
Chien-Chih
CC
Chiu
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 804, Taiwan, ROC. peichin1128@gmail.com.
Pei-Chin
PC
Chen
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804, Taiwan, ROC. betty8575@yahoo.com.tw.
Chiung-Yao
CY
Huang
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804, Taiwan, ROC. sheu@mail.nsysu.edu.tw.|Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC. sheu@mail.nsysu.edu.tw.|Department of Medical research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan, ROC. sheu@mail.nsysu.edu.tw.
Jyh-Horng
JH
Sheu
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 804, Taiwan, ROC. wzh@mail.nsysu.edu.tw.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 804, Taiwan, ROC. wzh@mail.nsysu.edu.tw.
Zhi-Hong
ZH
Wen
D000818:Animals; D002074:Butanones / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D066298:In Vitro Techniques; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental; D020460:Melanosomes / Q000378:metabolism*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D013440:Sulfides / Q000494:pharmacology* / Q000633:toxicity; D015027:Zebrafish
C000606757:4-(phenylsulfanyl)butan-2-one; D002074:Butanones; D008543:Melanins; D013440:Sulfides; D014442:Monophenol Monooxygenase
4-(phenylsulfanyl)butan-2-one; melanogenesis; melanosome maturation; tyrosinase; zebrafish