Acacetin (5,7-dihydroxy-4'-methoxyflavone) exhibits in vitro and in vivo anticancer activity through the suppression of NF-κB/Akt signaling in prostate cancer cells

Kim,Hye Ri; Park,Chan Gi; Jung,Ji Youn

doi:10.3892/ijmm.2013.1571

Acacetin (5,7-dihydroxy-4'-methoxyflavone) exhibits in vitro and in vivo anticancer activity through the suppression of NF-κB/Akt signaling in prostate cancer cells

Authors:
- Hye Ri Kim
- Chan Gi Park
- Ji Youn Jung
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Affiliations: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 340-702, Republic of Korea, Department of Rural Construction Engineering, Kongju National University, Yesan 340-702, Republic of Korea
Published online on: November 27, 2013 https://doi.org/10.3892/ijmm.2013.1571
Pages: 317-324

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Abstract

Acacetin (5,7-dihydroxy-4'-methoxyflavone) is a flavonoid compound with antimutagenic, antiplasmodial, antiperoxidant, anti-inflammatory and anticancer effects. However, the molecular targets and pathways underlying the anticancer effects of acacetin are yet to be elucidated. In this study, we investigated whether acacetin induces apoptosis in the human prostate cancer cell line, DU145. The results of 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays revealed that cell viability decreased in a dose- and time-dependent manner in response to acacetin. 4',6-Diamidino-2-phenylindole (DAPI) staining revealed that chromatin condensation significantly increased in a dose-dependent manner. Flow cytometric analysis indicated that acacetin suppressed the viability of DU145 cells by inducing apoptosis. Western blot anlaysis of various markers of signaling pathways revealed that acacetin targets the Akt and nuclear factor (NF)-κB signaling pathways by inhibiting the phosphorylation of IκBα and NF-κB in a dose-dependent manner. Consistent with its ability to induce apoptosis, the acacetin-mediated inhibition of the pro-survival pathway, Akt, and of the NF-κB pathway was accompanied by a marked reduction in the levels of the NF-κB‑regulated anti-apoptotic proteins, Bcl-2 and X-linked inhibitor of apoptosis protein (XIAP), as well as of the proliferative protein, cyclooxygenase (COX)-2. We further evaluated the effects of acacetin on prostate cancer using mice subcutaneously injected with DU145 prostate cancer cells. The acacetin-treated nude mice bearing DU145 tumor xenografts exhibited significantly reduced tumor size and weight, due to the effects of acacetin on cancer cell apoptosis, as determined by terminal deoxyribonucleotide transferase-mediated dUTP nick end-labeling (TUNEL) assay. Our findings suggest that acacetin exerts antitumor effects by targeting the Akt/NF-κB signaling pathway. Rurther investigations on this flavonoid are warranted to evaluate its potential use in the prevention and therapy of prostate cancer.

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