Ent-Peniciherqueinone Suppresses Acetaldehyde-Induced Cytotoxicity and Oxidative Stress by Inducing ALDH and Suppressing MAPK Signaling

Oh, Taehoon; Kwon, Mincheol; Yu, Jae Sik; Jang, Mina; Kim, Gun-Hee; Kim, Ki‐Hyun; Ko, Sung-Kyun; Ahn, Jong Seog

doi:10.3390/pharmaceutics12121229

Cited by 8 publications

(4 citation statements)

References 33 publications

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“…In tumors, evidence points to that ALDHs such as ALDH1A1, ALDH1A3, and ALDH3A1 are critical drivers of chemotherapeutic and radiotherapeutic resistance in many solid tumors by detoxifying cytotoxic drugs and mitigating oxidative stress 23,27 . For example, silencing of the ALDH1A1 gene in human breast cancer cells increases their sensitivity to paclitaxel by triggering the production of ROS, and similar results are obtained with other anticancer agents such as doxorubicin, sorafenib, and staurosporine 28 .…”

Section: Functions Of Aldhs In Diseasementioning

confidence: 77%

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

Xia

Liu

et al. 2023

MedComm

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The family of aldehyde dehydrogenases (ALDHs) contains 19 isozymes and is involved in the oxidation of endogenous and exogenous aldehydes to carboxylic acids, which contributes to cellular and tissue homeostasis. ALDHs play essential parts in detoxification, biosynthesis, and antioxidants, which are of important value for cell proliferation, differentiation, and survival in normal body tissues. However, ALDHs are frequently dysregulated and associated with various diseases like Alzheimer's disease, Parkinson's disease, and especially solid tumors. Notably, the involvement of the ALDHs in tumor progression is responsible for the maintenance of the stem‐cell‐like phenotype, triggering rapid and aggressive clinical progressions. ALDHs have captured increasing attention as biomarkers for disease diagnosis and prognosis. Nevertheless, these require further longitudinal clinical studies in large populations for broad application. This review summarizes our current knowledge regarding ALDHs as potential biomarkers in tumors and several non‐tumor diseases, as well as recent advances in our understanding of the functions and underlying molecular mechanisms of ALDHs in disease development. Finally, we discuss the therapeutic potential of ALDHs in diseases, especially in tumor therapy with an emphasis on their clinical implications.

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Section: Functions Of Aldhs In Diseasementioning

confidence: 77%

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

Xia

Liu

et al. 2023

MedComm

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“…Beyond β-adrenoceptor blockade, CAR has various roles, including antioxidant and antiproliferative activities, contributing to its anticancer effects [34]. We hypothesized that CAR's anticancer action might involve targeting ALDH, a detoxifying enzyme that mitigates oxidative stress, leading to therapeutic resistance in many solid tumors [41,73,74]. Genetic knockdown or pharmacological inhibition of ALDH1A1 in lung cancer enhances oxidative stress and sensitivity to chemotherapy [41].…”

Section: Discussionmentioning

confidence: 99%

Investigating Carvedilol’s Repurposing for the Treatment of Non-Small Cell Lung Cancer via Aldehyde Dehydrogenase Activity Modulation in the Presence of β-Adrenergic Agonists

Ikhmais,

Hammad,

Abusara

et al. 2023

CIMB

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Repurposing existing drugs appears to be a potential solution for addressing the challenges in the treatment of non-small cell lung cancer (NSCLC). β-adrenoceptor antagonist drugs (β-blockers) have tumor-inhibiting effects, making them promising candidates for potential NSCLC treatment. This study investigates the anticancer potential of a subset of β-blockers in NSCLC cell lines; A549 and H1299. Additionally, it investigates the underlying mechanism behind β-blockers’ anticancer effect by influencing a potential novel target named aldehyde dehydrogenase (ALDH). The MTT assay assessed β-blockers’ cytotoxicity on both cell lines, while Western blot and NADH fluorescence assays evaluated their influence on ALDH protein expression and activity. Carvedilol (CAR) was the most effective blocker in reducing cell survival of A549 and H1299 with IC50 of 18 µM and 13.7 µM, respectively. Significantly, CAR led to a 50% reduction in ALDH expression and 80% decrease in ALDH activity in A549 cells, especially when combined with β-agonists, in comparison to the control. This effect might be attributed to β-agonist blockade or an alternative pathway. This novel finding adds to our understanding of CAR’s multifaceted anticancer properties, implying that combining CAR with β-agonists could be a useful strategy for lung cancer treatment.

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“…Specifically, the binding of acetaldehyde to GSH inhibits the scavenging function of hydrogen peroxide, thereby exacerbating oxidative stress and lipid peroxidation [ 51 ]. Additionally, Oh et al showed that acetaldehyde induced an increase in p38 and JNK phosphorylation in PC12 cells, while penicillin reversed these reactions and prevented oxidative stress caused by acetaldehyde [ 52 ]. Farfan Labonne et al also demonstrated that acetaldehyde reduced the ATP content, respiratory control, superoxide dismutase (SOD) activity, and glutathione/oxidized GSH ratio [ 53 ].…”

Section: Mechanisms Of Ethanol-induced Liver Diseasesmentioning

confidence: 99%

Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

Yan

et al. 2023

J Transl Med

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Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being the leading cause of chronic liver disease. Many metabolic enzymes, including alcohol dehydrogenases such as ADH, CYP2E1, and CATacetaldehyde dehydrogenases ALDHsand nonoxidative metabolizing enzymes such as SULT, UGT, and FAEES, are involved in the metabolism of ethanol, the main component in alcoholic beverages. Ethanol consumption changes the functional or expression profiles of various regulatory factors, such as kinases, transcription factors, and microRNAs. Therefore, the underlying mechanisms of ALD are complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, and oxidative stress. Moreover, recent evidence has demonstrated that the gut-liver axis plays a critical role in ALD pathogenesis. For example, ethanol damages the intestinal barrier, resulting in the release of endotoxins and alterations in intestinal flora content and bile acid metabolism. However, ALD therapies show low effectiveness. Therefore, this review summarizes ethanol metabolism pathways and highly influential pathogenic mechanisms and regulatory factors involved in ALD pathology with the aim of new therapeutic insights.

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Ent-Peniciherqueinone Suppresses Acetaldehyde-Induced Cytotoxicity and Oxidative Stress by Inducing ALDH and Suppressing MAPK Signaling

Cited by 8 publications

References 33 publications

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets

Investigating Carvedilol’s Repurposing for the Treatment of Non-Small Cell Lung Cancer via Aldehyde Dehydrogenase Activity Modulation in the Presence of β-Adrenergic Agonists

Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease

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