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Open AccessArticle

Suppression of Nrf2 Activity by Chestnut Leaf Extract Increases Chemosensitivity of Breast Cancer Stem Cells to Paclitaxel

1, 1,* and 1,2,*
School of Food Science and Biotechnology (BK21 Plus), Kyungpook National University, Daegu 41566, Korea
Institute of Agricultural Science & Technology, Kyungpook National University, Daegu 41566, Korea
Authors to whom correspondence should be addressed.
Nutrients 2017, 9(7), 760;
Received: 18 May 2017 / Revised: 11 July 2017 / Accepted: 13 July 2017 / Published: 18 July 2017
(This article belongs to the Special Issue Selected Papers from APNNO Biennial Conference 2016)
PDF [2946 KB, uploaded 18 July 2017]


Due to metastatic potential and drug resistance, cancer stem cells (CSCs) have become a critical target for the development of chemotherapeutic agents. Recent studies showed that CSCs highly express NF-E2-related factor 2 (Nrf2)-mediated antioxidant enzymes and thereby retain relatively low levels of reactive oxygen species (ROS). Since anticancer agents usually utilize ROS as an arsenal for killing cancer cells, we hypothesized that inhibition of Nrf2 activity could increase the sensitivity of CSCs to anticancer drugs, and thus enhancing their therapeutic efficacy. We found that MCF-7-derived CSCs with a CD44high/CD24low phenotype formed mammospheres and highly expressed Nrf2 compared to the adherent parental MCF-7 cells. In a separate experiment, we screened 89 different edible plant extracts for inhibitory activity against the Nrf2 signaling pathway by using an antioxidant response element (ARE)-luciferase assay system. Among those extracts, Castanea crenata (chestnut) leaf extract significantly decreased the nuclear translocation of Nrf2 and protein expression of antioxidant enzymes in MCF-7-derived CSCs. The combined treatment of the CSCs with chestnut leaf extract and paclitaxel resulted in more effective cell death than the treatment with paclitaxel alone. These findings suggest that the chestnut leaf extract or its constituents could increase the susceptibility of breast CSCs to an anticancer drug, paclitaxel, through inhibition of the Nrf2 signaling pathway, and could be utilized as an adjuvant for chemotherapy. View Full-Text
Keywords: breast cancer; cancer stem cell; Nrf2; drug resistance; Castanea crenata breast cancer; cancer stem cell; Nrf2; drug resistance; Castanea crenata

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Woo, Y.; Oh, J.; Kim, J.-S. Suppression of Nrf2 Activity by Chestnut Leaf Extract Increases Chemosensitivity of Breast Cancer Stem Cells to Paclitaxel. Nutrients 2017, 9, 760.

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