Proanthocyanidins isolated from the leaves of Photinia × fraseri block the cell cycle and induce apoptosis by inhibiting tyrosinase activity in melanoma cells

Tyrosinase is considered a molecular marker of melanoma, and few natural antitumor drugs targeting tyrosinase have been identified. In this study, proanthocyanidins (PAs) were isolated from the leaves of Photinia × fraseri and their structures were characterized by high performance liquid chromatogr...

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Bibliographic Details
Published in:Food & function 2021-05, Vol.12 (9), p.3978-3991
Main Authors: Song, Wei, Zhao, Ya-Ying, Ren, Yuan-Jing, Liu, Lu-Lu, Wei, Shu-Dong, Yang, Hai-Bo
Format: Article
Language:English
Subjects:
Apoptosis
Catechin
Cell cycle
Chelation
Drug delivery
Drug development
Epicatechin
High performance liquid chromatography
Inhibitors
Ionization
Ions
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Melanin
Melanoma
Microphthalmia-associated transcription factor
Photinia
Proanthocyanidins
Proteins
Quinones
Scientific imaging
Spectroscopy
Tyrosinase
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Summary:Tyrosinase is considered a molecular marker of melanoma, and few natural antitumor drugs targeting tyrosinase have been identified. In this study, proanthocyanidins (PAs) were isolated from the leaves of Photinia × fraseri and their structures were characterized by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and the effects of antityrosinase activity were investigated. The results showed that the basic structural units of PAs are composed of catechin and epicatechin and that oligomer is the main component. PAs exhibited better antityrosinase activity via chelation of copper ions and by disturbing o-quinone production. Furthermore, analyses of the cell cycle, apoptosis rate, and regulation of melanin protein expression revealed preliminarily that PAs could affect melanin production by downregulating microphthalmia transcription factor (MITF) expression and by inhibiting the activities of tyrosinase and tyrosinase related protein 1 (TRP-1), leading to cell cycle arrest and apoptosis of melanoma cells. Collectively, our study demonstrated that PAs are potential tyrosinase inhibitors and have good antimelanoma effects. These findings provide a theoretical support for the application of tyrosinase inhibitors and for further drug development.
ISSN:2042-6496
2042-650X
DOI:10.1039/d1fo00134e