Herbacetin suppresses cutaneous squamous cell carcinoma and melanoma cell growth by targeting AKT and ODC

Dong Joon Kim, Mee Hyun Lee, Kang Dong 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

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Article numberbgx082
Pages (from-to)1136-1146
Number of pages11
JournalCarcinogenesis
Volume38
Issue number11
DOIs
StatePublished - Nov 1 2017

Bibliographical note

Funding Information:
This work was supported by The Hormel Foundation and National Institutes of Health grants CA166011, CA187027, CA196639 and CA027502.

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