4.7 Article

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

Journal

FOOD & FUNCTION
Volume 12, Issue 9, Pages 3978-3991

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d1fo00134e

Keywords

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Funding

  1. Science and Technology Research Project of Hubei Provincial Education Department [D20191301]
  2. Key Scientific Research Projects of Colleges and Universities in Henan Province [21A180003]
  3. Henan University of Urban Construction Academic Technology Leader Program [xs2019006-HY]

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This study isolated proanthocyanidins (PAs) from Photinia x fraseri leaves and found that PAs exhibited strong antityrosinase activity by chelating copper ions and disturbing o-quinone production. PAs are composed mainly of catechin and epicatechin, with oligomers as the main component. Additionally, PAs were shown to affect melanin production by downregulating MITF expression and inhibiting tyrosinase and TRP-1 activities, leading to cell cycle arrest and apoptosis of 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 x 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.

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