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.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Kim DJ,Lee MH,Liu K,Lim DY,Roh E,Chen H,Kim SH,Shim JH,Kim MO,Li W,Ma F,Fredimoses M,Bode AM,Dong Zdoi
10.1093/carcin/bgx082subject
Has Abstractpub_date
2017-10-26 00:00:00pages
1136-1146issue
11eissn
0143-3334issn
1460-2180pii
4210261journal_volume
38pub_type
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