Honokiol Inhibits Melanoma Growth by Targeting Keratin 18 in vitro and in vivo.

Tingting Liu,Zigang Dong,Ran Yang,Penglei Wang,Hui Liu,Kangdong Liu,Yamei Hu,Fangfang Liu,Hong Gyum Kim

doi:10.3389/fcell.2020.603472

Tingting Liu, Zigang Dong + Show 7 more

Open Access

https://doi.org/10.3389/fcell.2020.603472

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Abstract

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.

Highlights

Melanoma as an aggressive cancer with poor prognosis is responsible for most number of skin cancer related deaths
Our study demonstrates that keratin 18 (KRT18) plays an oncogenic role in melanoma and promotes melanoma growth, while honokiol can be an inhibitor for KRT18
The results showed that honokiol significantly suppressed the anchorage-independent growth of the melanoma cells (Figure 1A)

Summary

Introduction

Melanoma as an aggressive cancer with poor prognosis is responsible for most number of skin cancer related deaths. According to the American Cancer Society, it is estimated that 1,00,350 new melanoma cases, and 6,850 related deaths will occur in the United States alone, in 2020 (American Cancer Society, 2020). The melanoma incidences continue to increase worldwide, and it is the fifth most common cancer in men and sixth most common cancer in women in the United States (Carr et al, 2020). It was estimated that the death rates remain to be stable, whereas, the annual cost of treating newly diagnosed melanoma cases to increase from $457 million in 2011 to $1.6 billion in 2030 (Guy et al, 2015). Substantial reductions in the melanoma incidences, mortalities, and treatment cost can be achieved by comprehensive interventions including reduced UV radiation exposure and increased sun protection. There is an urgent need to discover novel effective therapeutic targets and inhibitors to suppress the tumor progression and aid in the chemoprevention of melanoma

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