N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells

Abstract

Pancreatic cancer is a common cause of worldwide cancer-related mortality with a poor 5-year survival rate. Aldehyde dehydrogenase (ALDH) activity is a possible marker for malignant stem cells in solid organ systems, including the pancreas, and N,N-diethylaminobenzaldehyde (DEAB) is able to inhibit ALDH activity. In the present study, the role of DEAB in the treatment of pancreatic cancer cells and the potential underlying mechanisms were investigated. The ALDH activities of pancreatic cancer cell lines treated with or without DEAB were analyzed by an ALDEFLUOR™ assay. The Cell Counting Kit-8 and colony formation assays, and cell cycle analysis were used to evaluate the viability, colony-forming ability and cell quiescence of cell lines under DEAB treatment, respectively. DEAB and/or gemcitabine-induced cell apoptosis was assessed by flow cytometry. DEAB reduced ALDH activity and inhibited the proliferation, colony-forming ability and cell quiescence of pancreatic cancer cell lines. Compared with respective controls, DEAB alone and the combination of gemcitabine and DEAB significantly decreased cell viability and increased cell apoptosis. Moreover, reverse transcription-PCR and western blotting were used to measure the expressions of B cell lymphoma 2 (Bcl2) associated X protein (Bax) and Bcl2 mRNA and protein. The anti-cancer effect of DEAB was associated with upregulation of Bax expression. Therefore, targeting ALDH with DEAB may be a potential therapeutic choice for pancreatic cancer, demonstrating a synergic effect with gemcitabine.

Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells

“…Furthermore, endometrial spheres obtained under DEAB influence during the five-day sphere-formation protocol exhibited a significant decrease in the projection area (Figure 2b), suggesting a potential impact on CSC proliferation. Similar effects of DEAB on the proliferation and colony-forming capacity were observed in pancreatic cells [44].…”

The pro- and antineoplastic effects of deoxycholic acid in pancreatic adenocarcinoma cell models

“…ALDH1 is a cancer stem cell marker in some tumors [ 28 , 29 ], including pancreatic adenocarcinoma [ 30 , 31 ]. We assessed ALDH1 activity after DCA treatment in Capan-2 cells using the aldefluor assay.…”

Expansion of the 4-(Diethylamino)benzaldehyde Scaffold to Explore the Impact on Aldehyde Dehydrogenase Activity and Antiproliferative Activity in Prostate Cancer

“…Identification of CSCs is frequently carried out using the Aldefluor assay, which includes the addition of 4-(diethylamino)­benzaldehyde (DEAB), a small-molecule inhibitor that is used as a control to identify subpopulations of cells with high ALDH expression (ALDH high ) and with SC-like properties . DEAB is a pan-ALDH inhibitor, which has been found to delay differentiation of CSCs, , also showing potential in combination treatments with other drugs. − Early work showed that 4-(dipropylamino)­benzaldehyde was more potent than DEAB as a reversible inhibitor against mouse and human ALDH1, with variable inhibitory effects according to the selected substrate . In the same study, 4-(dimethylamino)­benzaldehyde and 4-(dibutylamino)­benzaldehyde showed low binding affinity to ALDH1 but provided no information on isoform selectivity .…”