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Title: Combination treatment with highly bioavailable curcumin and NQO1 inhibitor exhibits potent antitumor effects on esophageal squamous cell carcinoma
Authors: Mizumoto, Ayaka
Ohashi, Shinya  kyouindb  KAKEN_id
Kamada, Mayumi
Saito, Tomoki
Nakai, Yukie
Baba, Kiichiro
Hirohashi, Kenshiro
Mitani, Yosuke
Kikuchi, Osamu  kyouindb  KAKEN_id  orcid (unconfirmed)
Matsubara, Junichi
Yamada, Atsushi  kyouindb  KAKEN_id
Takahashi, Tsukasa
Lee, Hyunjin
Okuno, Yasushi  kyouindb  KAKEN_id
Kanai, Masashi
Muto, Manabu  kyouindb  KAKEN_id
Author's alias: 廣橋, 研志郎
松原, 淳一
山田, 敦
奥野, 恭史
金井, 雅史
武藤, 学
Keywords: Esophageal squamous cell carcinoma
NQO1 inhibitor
Issue Date: 5-Aug-2019
Publisher: Springer Nature
Journal title: Journal of Gasatroenterology
Volume: 54
Start page: 687
End page: 698
Abstract: Background: Esophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. Curcumin, a polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. Theracurmin® (THC) is a highly bioavailable curcumin dispersed with colloidal submicron particles. Methods: We examined antitumor effects of THC on ESCC cells by cell viability assay, colony and spheroid formation assay, and xenograft models. To reveal its mechanisms, we investigated the levels of reactive oxygen species (ROS) and performed microarray gene expression analysis. According to those analyses, we focused on NQO1, which involved in the removal of ROS, and examined the effects of NQO1-knockdown or overexpression on THC treatment. Moreover, the therapeutic effect of THC and NQO1 inhibitor on ESCC patient-derived xenografts (PDX) was investigated. Results: THC caused cytotoxicity in ESCC cells, and suppressed the growth of xenografted tumors more efficiently than curcumin. THC increased ROS levels and activated the NRF2–NMRAL2P–NQO1 expressions. Inhibition of NQO1 in ESCC cells by shRNA or NQO1 inhibitor resulted in an increased sensitivity of cells to THC, whereas overexpression of NQO1 antagonized it. Notably, NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC PDX tumors. Conclusions: These findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC.
Rights: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
DOI(Published Version): 10.1007/s00535-019-01549-x
PubMed ID: 30737573
Appears in Collections:Journal Articles

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