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Carcinogenesis. 2017 Oct 26;38(11):1136-1146. doi: 10.1093/carcin/bgx082.

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

Author information

1
China-US (Henan) Hormel Cancer Institute, Zhengzhou, Henan 450008, China.
2
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA.
3
The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan 450008, China.
4
The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, Henan, China.
5
The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, China.
6
College of Pharmacy, Mokpo National University, Muan-gun, Jeonnam 534-729, Republic of Korea.
7
Center for Laboratory Animal Resources, School of Animal Biotechnology, Kyungpook National University, Dae-gu 700-842, Republic of Korea.

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.

PMID:
29029040
PMCID:
PMC5862242
DOI:
10.1093/carcin/bgx082
[Indexed for MEDLINE]
Free PMC Article

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