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Herbacetin Suppresses Cutaneous Squamous Cell Carcinoma and Melanoma Cell Growth by Targeting AKT and ODC

Herbacetin Suppresses Cutaneous Squamous Cell Carcinoma and Melanoma Cell Growth by Targeting AKT and ODC

Dong Joon Kim, Mee-Hyun Lee, KangDong Liu, Do Young Lim, Eunmiri Roh, Hanyong Chen, Sung-Hyun Kim, Jung-Hyun Shim, Myoung Ok Kim, Wenwen Li, Fayang Ma, Mangaladoss Fredimoses, Ann M Bode, Zigang Dong

Carcinogenesis. 2017 Oct 26;38(11):1136-1146.

PMID: 29029040

Abstract:

Herbacetin is a flavonol compound that is found in plants such as flaxseed and ramose scouring rush herb, it possesses a strong antioxidant capacity, and exerts anticancer effects on colon and breast cancer. However, the effect of herbacetin on skin cancer has not been investigated. Herein, we identified herbacetin as a dual V-akt murine thymoma viral oncogene homolog (AKT) and ornithine decarboxylase (ODC) inhibitor, and illustrated its anticancer effects in vitro and in vivo against cutaneous squamous cell carcinoma (SCC) and melanoma cell growth. To identify the direct target(s) of herbacetin, we screened several skin cancer-related protein kinases, and results indicated that herbacetin strongly suppresses both AKT and ODC activity. Results of cell-based assays showed that herbacetin binds to both AKT and ODC, inhibits TPA-induced neoplastic transformation of JB6 mouse epidermal cells, and suppresses anchorage-independent growth of cutaneous SCC and melanoma cells. The inhibitory activity of herbacetin was associated with markedly reduced NF-κB and AP1 reporter activity. Interestingly, herbacetin effectively attenuated TPA-induced skin cancer development and also exhibited therapeutic effects against solar-UV-induced skin cancer and melanoma growth in vivo. Our findings indicate that herbacetin is a potent AKT and ODC inhibitor that should be useful for preventing skin cancers.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP527957	Herbacetin		527-95-7	Price

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