title: Aberrant expression of redox protein Ape1 in colon cancer stem cells.
abstract: Ape1 is an important redox protein, essential for specific cytokine-induced signal transduction. Ape1 signaling is also important in regulating the growth of cancer cells, including colon cancer cells. The present study investigated whether Ape1 signaling plays a role in the regulation of colon cancer stem cell (CCSC) growth. The results showed that Ape1 was aberrantly expressed in CCSCs, as determined by quantitative (q)PCR assay. A laser confocal microscopy assay demonstrated that the Ape1 protein was mainly distributed in the nuclei, but not the cytoplasm, of the CSCs. Treatment of CCSCs with Ape1 redox inhibitor (E3330) significantly affected growthin vitro. In colon cancer xenograft mice,in vivoadministration of E3330 enhanced tumor responses to the chemotherapeutic drug, 5-fluorouracil (5-FU). Furthermore, the combination of E3330 and 5-FU evidently increased the cytotoxicity of 5-FU in CSC growth. In the qPCR assay, the CCSCs were demonstrated to express the dominant ATP-binding cassette sub-family G member 2 (ABC-G2), but not the multidrug resistance 1, genes. Thus, we hypothesized that drug resistance in CCSCs is mediated by ABC-G2. Since CSCs are involved in cancer metastasis, the Ape1 inhibitor may be a potential agent in the inhibition of colon cancer growth and metastasis.
authors.affiliation: Department of Pharmacy, Shanghai Eighth People's Hospital, Shanghai 200235, P.R. China.
authors.forename: Debao
authors.initials: D
authors.lastname: Lou
authors.affiliation: Department of Ophthalmology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Ding
authors.affiliation: Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Dai
authors.affiliation: Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai 200240, P.R. China ; Shanghai Institute for Pediatrics Research, Xin Hua Hospital, Shanghai Jiao Tong University Shanghai of Medicine, Shanghai 200092, P.R. China.
authors.forename: Gang-Ming
authors.initials: GM
authors.lastname: Zou
keywords: 5-fluorouracil; ABC-G2; E3330; MDR1; Ref-1; colon cancer