Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivo
Honokiol, a natural compound, derived from Magnolia officinalis, has been shown to have anti-cancer effect in several cancer types. However, the underlying molecular mechanism associated with its anti-cancer properties has not been fully elucidated. In the current study, we showed that honokiol inhi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2020.603472/full |
| _version_ | 1819206660109893632 |
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| author | Tingting Liu Tingting Liu Hui Liu Hui Liu Penglei Wang Penglei Wang Yamei Hu Yamei Hu Ran Yang Fangfang Liu Fangfang Liu Hong Gyum Kim Zigang Dong Zigang Dong Zigang Dong Kangdong Liu Kangdong Liu Kangdong Liu Kangdong Liu Kangdong Liu |
| author_facet | Tingting Liu Tingting Liu Hui Liu Hui Liu Penglei Wang Penglei Wang Yamei Hu Yamei Hu Ran Yang Fangfang Liu Fangfang Liu Hong Gyum Kim Zigang Dong Zigang Dong Zigang Dong Kangdong Liu Kangdong Liu Kangdong Liu Kangdong Liu Kangdong Liu |
| author_sort | Tingting Liu |
| collection | DOAJ |
| description | Honokiol, a natural compound, derived from Magnolia officinalis, has been shown to have anti-cancer effect in several cancer types. However, the underlying molecular mechanism associated with its anti-cancer properties has not been fully elucidated. In the current study, we showed that honokiol inhibited the growth of melanoma cells in a dose and time-dependent manner. Mechanistically, it directly interacts with keratin 18 (KRT18) protein and induces its degradation through ubiquitination. Furthermore, the expression of KRT18 was found to be higher in melanoma tissues compared to the normal skin tissues. In addition, KRT18 overexpression significantly promoted melanoma cell proliferation and growth. Our results showed that honokiol treatment significantly decreased KRT18 protein level and suppressed the tumor growth in melanoma cell-derived xenograft mice models. Hence, KRT18 plays an oncogenic role in melanoma and honokiol can be an inhibitor for KRT18. |
| first_indexed | 2024-12-23T05:11:07Z |
| format | Article |
| id | doaj.art-02fd30b4ad8a4a9b9c0bdc0cd8512834 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-23T05:11:07Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-02fd30b4ad8a4a9b9c0bdc0cd85128342022-12-21T17:58:58ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.603472603472Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivoTingting Liu0Tingting Liu1Hui Liu2Hui Liu3Penglei Wang4Penglei Wang5Yamei Hu6Yamei Hu7Ran Yang8Fangfang Liu9Fangfang Liu10Hong Gyum Kim11Zigang Dong12Zigang Dong13Zigang Dong14Kangdong Liu15Kangdong Liu16Kangdong Liu17Kangdong Liu18Kangdong Liu19Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, ChinaHenan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, ChinaDepartment of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaChina-US (Henan) Hormel Cancer Institute, Zhengzhou, ChinaHenan Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, ChinaState Key Laboratory for the Prevention and Treatment of Esophageal Cancer, Zhengzhou University, Zhengzhou, ChinaCancer Chemoprevention International Collaboration Laboratory, Zhengzhou, ChinaHonokiol, a natural compound, derived from Magnolia officinalis, has been shown to have anti-cancer effect in several cancer types. However, the underlying molecular mechanism associated with its anti-cancer properties has not been fully elucidated. In the current study, we showed that honokiol inhibited the growth of melanoma cells in a dose and time-dependent manner. Mechanistically, it directly interacts with keratin 18 (KRT18) protein and induces its degradation through ubiquitination. Furthermore, the expression of KRT18 was found to be higher in melanoma tissues compared to the normal skin tissues. In addition, KRT18 overexpression significantly promoted melanoma cell proliferation and growth. Our results showed that honokiol treatment significantly decreased KRT18 protein level and suppressed the tumor growth in melanoma cell-derived xenograft mice models. Hence, KRT18 plays an oncogenic role in melanoma and honokiol can be an inhibitor for KRT18.https://www.frontiersin.org/articles/10.3389/fcell.2020.603472/fullhonokiolkeratin18degradationubiquitinationmelanoma |
| spellingShingle | Tingting Liu Tingting Liu Hui Liu Hui Liu Penglei Wang Penglei Wang Yamei Hu Yamei Hu Ran Yang Fangfang Liu Fangfang Liu Hong Gyum Kim Zigang Dong Zigang Dong Zigang Dong Kangdong Liu Kangdong Liu Kangdong Liu Kangdong Liu Kangdong Liu Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivo Frontiers in Cell and Developmental Biology honokiol keratin18 degradation ubiquitination melanoma |
| title | Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivo |
| title_full | Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivo |
| title_fullStr | Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivo |
| title_full_unstemmed | Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivo |
| title_short | Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivo |
| title_sort | honokiol inhibits melanoma growth by targeting keratin 18 in vitro and in vivo |
| topic | honokiol keratin18 degradation ubiquitination melanoma |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2020.603472/full |
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