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10.1016/j.amjsurg.2014.09.014

http://scihub22266oqcxt.onion/10.1016/j.amjsurg.2014.09.014
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suck abstract from ncbi


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pmid25450590      Am+J+Surg 2014 ; 208 (6): 995-1002
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  • Honokiol affects melanoma cell growth by targeting the AMPK signaling pathway #MMPMID25450590
  • Kaushik G; Kwatra D; Subramaniam D; Jensen RA; Anant S; Mammen JM
  • Am J Surg 2014[Dec]; 208 (6): 995-1002 PMID25450590show ga
  • 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 officianalis, 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 (CSCs) was 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 ultra-low attachment plates. Results: HNK is highly effective in inhibiting melanoma cells by attenuating AKT/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 ATP pool in a dose-dependent manner with maximum effects observed at 48 h. Conclusion: 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.
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