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Honokiol affects melanoma cell growth by targeting the AMP-activated protein kinase signaling pathway.

Abstract：

BACKGROUND:Malignant melanoma is an aggressive form of skin cancer with limited effective therapeutic options. Melanoma research concentrates on maximizing the effect on cancer cells with minimal toxicity to normal cells. AMP-activated protein kinase (AMPK) is an important regulator of cellular energy homeostasis and has been shown to control tumor progression regulating the cell cycle, protein synthesis, and cell growth and/or survival. Honokiol (HNK) is a biphenolic compound derived from Magnolia officinalis, a plant that has been used in traditional Chinese and Japanese medicine for the treatment of various pathological conditions. Recent studies have shown that HNK has antitumor activity with relatively low toxicity. In this study, we demonstrated that the growth inhibitory effects of HNK on melanoma and melanoma cancer stem cells were mediated through the activation of AMPK and hence AMPK signaling in melanoma cells. METHODS:We determined the effects of HNK treatment on various melanoma cell lines. HNK-induced cell growth inhibitory effects were determined using hexosaminidase assay. Protein expression studies were done by immunoblotting. Primary spheroid assay was used to assess stemness by growing single suspension cells in ultralow attachment plates. RESULTS:HNK is highly effective in inhibiting melanoma cells by attenuating protein kinase B/mammalian target of rapamycin and AMPK signaling. HNK showed significant inhibition of the spheroid-forming capacity of melanoma cells and, hence, stemness. HNK significantly decreased the number and size of melanospheres in a dose-dependent manner. Western blot analyses showed enhanced phosphorylation of AMPK in melanoma cells. Furthermore, HNK decreased the cellular adenosine triphosphate pool in a dose-dependent manner with maximum effects observed at 48 hours. CONCLUSIONS:The results suggest that HNK can target melanoma cells and mark them for cell death through AMPK signaling. Further studies are warranted for developing HNK as an effective chemopreventive/therapeutic agent in melanoma.

journal_name

Am J Surg

journal_title

American journal of surgery

authors

Kaushik G,Kwatra D,Subramaniam D,Jensen RA,Anant S,Mammen JM

doi

10.1016/j.amjsurg.2014.09.014

subject

Has Abstract

pub_date

2014-12-01 00:00:00

pages

995-1002; discussion 1001-2

issue

eissn

0002-9610

issn

1879-1883

pii

S0002-9610(14)00458-9

journal_volume

208

pub_type

杂志文章

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Honokiol affects melanoma cell growth by targeting the AMP-activated protein kinase signaling pathway.