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Biosci Biotechnol Biochem. 2018 Dec;82(12):2064-2071. doi: 10.1080/09168451.2018.1514246. Epub 2018 Sep 5.

Citrus peel polymethoxyflavones, sudachitin and nobiletin, induce distinct cellular responses in human keratinocyte HaCaT cells.

Author information

1
a Department of Biological Science and Technology , Tokushima University Graduate School , Tokushima , Japan.
2
b Laboratory of Nutritional Science, Department of Food Science and Nutrition , Shikoku Junior College , Tokushima , Japan.
3
c Department of Bioscience and Bioindustry , Tokushima University Graduate School , Tokushima , Japan.

Abstract

A variety of polyphenols have been isolated from plants, and their biological activities have been examined. Sudachitin (5,7,4'-trihydroxy-6,8,3'-trimethoxyflavone) is a polymethoxyflavone that is isolated from the peel of Citrus sudachi. Although we previously reported that sudachitin possesses an anti-inflammatory activity, its other biological activities are not yet understood. In this study, we report a novel biological activity of sudachitin, which selectively induced apoptosis in human keratinocyte HaCaT cells. Another polymethoxyflavone, nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), promoted autophagy but not apoptosis in HaCaT cells. On the other hand, 3'-demethoxysudachitin (5,7,4'-trihydroxy-6,8-dimethoxyflavone) failed to induce apoptosis and autophagy. These results show that three polymethoxyflavones have different effects on apoptosis and autophagy in HaCaT cells. Understanding the structure and biological activity of polymethoxyflavones may lead to the discovery of potential candidates for cancer drug development without significant toxic side effects. Abbreviations: ROS: reactive oxygen species; DMSO: dimethyl sulfoxide; MTT: 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; PARP: poly(ADP-ribose) polymerase; PI: propidium iodide; MAPK: mitogen-activated protein kinase.

KEYWORDS:

Polymethoxyflavone; apoptosis; autophagy

PMID:
30185129
DOI:
10.1080/09168451.2018.1514246
[Indexed for MEDLINE]

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