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Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

Ohnuma, Tomokazu ; Matsumoto, Takashi ; Itoi, Ayano ; Kawana, Ayako ; Nishiyama, Takahito ; Ogura, Kenichiro ; Hiratsuka, Akira

Biochemical and biophysical research communications, 2011-10, Vol.413 (4), p.623-629 [Periódico revisado por pares]

United States: Elsevier Inc

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Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract
Autor: Ohnuma, Tomokazu ; Matsumoto, Takashi ; Itoi, Ayano ; Kawana, Ayako ; Nishiyama, Takahito ; Ogura, Kenichiro ; Hiratsuka, Akira
Assuntos: 60 APPLIED LIFE SCIENCES ; Anticancer drugs ; Antineoplastic Agents - pharmacology ; ANTIOXIDANTS ; Antitumor agents ; BENZOQUINONES ; Cell Line, Tumor ; CHEMOTHERAPY ; Cinnamomi Cortex ; Cortex ; Cytotoxicity ; DETOXIFICATION ; DOXORUBICIN ; Doxorubicin - pharmacology ; Drug Resistance, Neoplasm - drug effects ; Drugs, Chinese Herbal - pharmacology ; ENZYME ACTIVITY ; ENZYMES ; Etoposide ; Etoposide - pharmacology ; GLUTATHIONE ; Humans ; INHIBITION ; Lung cancer ; Lung Neoplasms - metabolism ; LUNGS ; NAD ; NAD(P)H Dehydrogenase (Quinone) - antagonists & inhibitors ; NEOPLASMS ; NF-E2-Related Factor 2 - antagonists & inhibitors ; NF-E2-Related Factor 2 - metabolism ; Nrf2 ; Proanthocyanidins - pharmacology ; Procyanidin ; SENSITIVITY ; TRANSCRIPTION FACTORS
É parte de: Biochemical and biophysical research communications, 2011-10, Vol.413 (4), p.623-629
Notas: ObjectType-Article-2
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Descrição: ► We found a novel inhibitor of Nrf2 known as a chemoresistance factor. ► Overexpressed Nrf2 in lung cancer cells was suppressed by Cinnamomi Cortex extract. ► Cytotoxic action of anticancer drugs in cells treated with the extract was enhanced. ► Procyanidin tetramers and pentamers were active components in suppressing Nrf2. Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor because Nrf2-regulated enzymes play a key role in antioxidant and detoxification processes. Recent studies have reported that lung cancer cells overexpressing Nrf2 exhibit increased resistance to chemotherapy. Suppression of overexpressed Nrf2 is needed for a new therapeutic approach against lung cancers. In the present study, we found that Cinnamomi Cortex extract (CCE) has an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells with high Nrf2 activity. Moreover, we demonstrated that CCE significantly enhances sensitivity of A549 cells to the cytotoxic action of doxorubicin and etoposide as well as increasing the intracellular accumulation of both drugs. These results suggest that CCE might be an effective concomitant agent to reduce anticancer drug resistance derived from Nrf2 overexpression. Bioactivity-guided fractionation revealed that procyanidin tetramers and pentamers contained in CCE were active components in suppressing Nrf2.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

Ohnuma, Tomokazu ; Matsumoto, Takashi ; Itoi, Ayano ; Kawana, Ayako ; Nishiyama, Takahito ; Ogura, Kenichiro ; Hiratsuka, Akira

United States: Elsevier Inc

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