Inhibition of aldehyde dehydrogenase 1 enhances the cytotoxic effect of retinaldehyde on A549 cancer cells

Park, Jin Won; Jung, Kyung‐Ho; Lee, Jin Hee; Moon, Seung Hwan; Cho, Young Seok; Lee, Kyung-Han

doi:10.18632/oncotarget.19544

Cited by 15 publications

(13 citation statements)

References 32 publications

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“…In cholangiocarcinoma, the reduction of ALDH activity in gemcitabine-resistant cells by metronidazole resulted in the enhancement of chemosensitivity (23). In lung cancer, inhibiting ALDH with DEAB and disulfiram suppressed the viability of cancer cells and sensitized the cancer cells to chemotherapy (10,11). Consistent with these data, in the present study, after comparing untreated cells and cells treated with DEAB, it was observed that an ALDH inhibitor (DEAB) reduced cell viability, cell quiescence and furthermore, enhanced gemcitabine-induced cytotoxicity in vitro.…”

Section: Discussionsupporting

confidence: 90%

“…Aldehyde dehydrogenase (ALDH) is a family of enzymes involved in the metabolism of intracellular aldehydes to acids by an NAD(P) + dependent reaction (6). ALDH activity is regarded as a marker for both normal and malignant stem cells in the hematological system and in the solid organ system, including pancreas, lung, liver, breast, colon and ovary organs (6)(7)(8)(9)(10)(11)(12)(13). As an ALDH isoform, ALDH1 is a detoxifying enzyme responsible for oxidizing intracellular retinaldehyde to retinoic acid (6,10).…”

Section: Introductionmentioning

confidence: 99%

“…ALDH activity is regarded as a marker for both normal and malignant stem cells in the hematological system and in the solid organ system, including pancreas, lung, liver, breast, colon and ovary organs (6)(7)(8)(9)(10)(11)(12)(13). As an ALDH isoform, ALDH1 is a detoxifying enzyme responsible for oxidizing intracellular retinaldehyde to retinoic acid (6,10). N,N-diethylaminobenzaldehyde (DEAB), utilized as a negative control in an ALDEFLUOR™ assay, is generally considered as a selective ALDH1A1 inhibitor (12,14).…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Zheng

et al. 2020

Exp Ther Med

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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.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wang

Zheng

et al. 2020

Exp Ther Med

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“…Interestingly, our results also showed that TCS did not affect the expression of ALDH1A1, Apo E, ADRA2A, DPYD, COMT, TPMT, HTRA, or MTHFR, which all participate in drug resistance, but not by promoting drug metabolism or clearance. 31 – 40 These results confirmed the specificity of TCS function.…”

Section: Discussionsupporting

confidence: 72%

Triclosan treatment decreased the antitumor effect of sorafenib on hepatocellular carcinoma cells

Wu¹,

Zhuang²,

Zhang³

et al. 2018

OTT

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BackgroundTriclosan is a widely applied antimicrobial agent which affects the endocrine system and homeostasis; it may also promote the cirrhosis and hepatocellular carcinoma (HCC) growth in a mice model. The exact roles of triclosan in regulating human hepatocellular carcinoma development and treatment remain unknown.MethodsMHCC97-H, a highly aggressive HCC cell line, was treated with indicated concentration of triclosan or sorafenib. The expression of drug-resistance genes was examined by qPCR. The clearance or metabolism of sorafenib was determined by liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS). MTT assay was used to examine the MHCC97-H cell proliferation. Nude mice were used to exam the anti-tumor effect of sorafenib on subcutaneous and intrahepatic growth of MHCC97-H cells.ResultsIn the present study, triclosan could induce the expression of drug-resistance genes in MHCC97-H cells (a highly aggressive HCC cell line), accelerate the clearance of sorafenib, and attenuate the anti-proliferation effect of this molecular targeted agent in MHCC97-H cells. Triclosan decreased the antitumor effect of sorafenib on subcutaneous and intrahepatic growth of MHCC97-H in nude mice.ConclusionBy discovering the fact that triclosan treatment enhances sorafenib resistance in HCC cells, this work suggests exposure of triclosan is detrimental to HCC patients during chemotherapy.

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“…Acetaldehyde oxidation to acetate will produce NADH and its oxidation back to NAD + by the mitochondrial the respiratory chain will produce ROS (Zakhari, ). In addition, there is some controversy as to the antioxidant and prooxidant roles of retinoids and, specifically, retinaldehyde (Edge & Truscott, ; Keys & Zimmerman, ; Park et al, ). The recruitment of RALDH2 for acetaldehyde oxidation instead of retinoic acid production (Shabtai et al, ) would result in the accumulation of retinaldehyde with its suspected pro‐oxidant activity.…”

Section: The Etiology Of Fasdmentioning

confidence: 99%

Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder

Petrelli

Bendelac

Hicks

et al. 2019

Genesis

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Summary Fetal Alcohol Spectrum Disorder (FASD) is a set of neurodevelopmental malformations caused by maternal consumption of alcohol during pregnancy. FASD sentinel facial features are unique to the disorder, and microcephaly is common in severe forms of FASD. Retinoic acid deficiency has been shown to cause craniofacial malformations and microcephaly in animal models reminiscent of those caused by prenatal alcohol exposure. Alcohol exposure affects the migration and survival of cranial neural crest cells, which are required for proper frontonasal prominence and pharyngeal arch development. Defects in craniofacial development are further amplified by the many downstream pathways that are transcriptionally controlled retinoic acid target genes, including Shh signaling. Recent evidence shows that alcohol exposure itself is sufficient to induce retinoic acid deficiency in the embryo. These data suggest that retinoic acid deficiency is an important underlying etiology of FASD. In disorders like Vitamin A Deficiency, FASD, DiGeorge (22q11.2 Deletion Syndrome), CHARGE, Smith‐Magenis, Matthew‐Wood, and Congenital Zika Syndromes, evidence is accumulating to link reduced retinoic acid signaling with developmental defects like craniofacial malformations and microcephaly. Research focus on characterizing the effects of retinoic acid deficiency during early development and on understanding the downstream signaling pathways involved in aberrant head, and craniofacial development will reveal underlying etiologies of these disorders.

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Inhibition of aldehyde dehydrogenase 1 enhances the cytotoxic effect of retinaldehyde on A549 cancer cells

Cited by 15 publications

References 32 publications

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

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

Triclosan treatment decreased the antitumor effect of sorafenib on hepatocellular carcinoma cells

Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder

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