Aldehyde dehydrogenases and cancer stem cells

Xu, Xia; Chai, Shoujie; Wang, Pingli; Zhang, Chenchen; Yang, Yiming; Yang, Ying; Wang, Kai

doi:10.1016/j.canlet.2015.08.018

Cited by 178 publications

(134 citation statements)

References 109 publications

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“…ALDH has been proposed as a prognostic marker for many cancers including lung (45), breast (46), ovarian (47), pancreatic (24), and colon (48). There are many excellent recent reviews of ALDHs in cancer and CSCs (6,(49)(50)(51)(52) and these topics will not be discussed in detail here. ALDH has been most extensively studied in breast cancer where it correlates with tumor grade, ER negativity, HER2 positivity and poor patient survival (44,53,54).…”

Section: Figurementioning

confidence: 99%

Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets

2016

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Resistance to current chemotherapeutic or radiation-based cancer treatment strategies is a serious concern. Cancer stem cells (CSCs) are typically able to evade treatment and establish a recurrent tumor or metastasis, and it is these that lead to the majority of cancer deaths. Therefore, a major current goal is to develop treatment strategies that eliminate the resistant CSCs as well as the bulk tumor cells in order to achieve complete disease clearance. Aldehyde dehydrogenases (ALDHs) are important for maintenance and differentiation of stem cells as well as normal development. There is expanding evidence that ALDH expression increases in response to therapy and promotes chemoresistance and survival mechanisms in CSCs. This perspective will discuss a paper by

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Section: Figurementioning

confidence: 99%

Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets

2016

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“…In contrast to the native structure, however, little or no selectivity was found against aldehyde dehydrogenase positive cells (ALDH + ), a phenotype associated with CSC properties such as high tumorigenicity and increased migration. 46,47 Efficient synthesis of unsubstituted hydroxamic acids is challenging, in part due to the hydrolytic sensitivity of many such products. 48,49 In light of this and of the low accessibility of the carboxylate moiety of SA, 20 it is noteworthy that single step access to each of the targeted hybrid derivatives 5a−d could be attained (Scheme 1).…”

mentioning

confidence: 99%

Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids

Borgström

Huang

Chygorin

et al. 2016

ACS Med. Chem. Lett.

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The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N-and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the hydroxamic acid moiety to the metal ion. A crystal structure of an cationic sodium complex with a noncoordinating anion corroborates this finding and, moreover, reveals a novel type of hydrogen bond network that stabilizes the head-to-tail conformation that encapsulates the cation analogously to the native structure. The hydroxamic acid derivatives display down to single digit micromolar activity against cancer cells but unlike salinomycin selective reduction of ALDH + cells, a phenotype associated with cancer stem cells was not observed. Mechanistic implications are discussed.

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“…ALDH1A1 and ALDH2 primarily metabolize acetaldehyde to acetate. ALDH activity maintains a low ROS level and inhibits CSC apoptosis [99]. Reactive aldehydes' metabolism and the ROS level are closely related to the characteristics of CSCs and cancer development.…”

Section: Aldh1 In Acetaldehyde Metabolismmentioning

confidence: 99%

Cancer Stem Cells and Aldehyde Dehydrogenase 1 in Liver Cancers

Tomita¹,

Kanayama²,

Niwa³

et al. 2017

Updates in Liver Cancer

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The cancer stem cell (CSC) theory posits that a small population of cells with stem celllike features is responsible for tumor growth, resistance, and recurrence in many malignancies. This theory could be a useful paradigm for designing innovative targeted drug therapies. Liver cancer is the ifth most common cancer worldwide, with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) as the predominant forms. Hepatic stem/progenitor cells are believed to be the origin of HCCs and CCAs; however, this remains a controversial topic. Aldehyde dehydrogenase (ALDH) is the main enzymatic system responsible for the clearance of acetaldehyde from the hepatocytes in the liver tissue. Therefore, ALDH1 has been suggested to be a potential, biological and CSC marker in liver cancers. We here provide an overview of the current state of knowledge of CSCs in liver and the role of ALDH1 in the development and progression of liver cancers and discuss its potential value as a prognostic and diagnostic biomarker.

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Aldehyde dehydrogenases and cancer stem cells

Cited by 178 publications

References 109 publications

Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets

Aldehyde dehydrogenases in cancer stem cells: potential as therapeutic targets

Salinomycin Hydroxamic Acids: Synthesis, Structure, and Biological Activity of Polyether Ionophore Hybrids

Cancer Stem Cells and Aldehyde Dehydrogenase 1 in Liver Cancers

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