Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway

Cao, Wenqiang; Zhai, Xiaoyu; Ma, Jiwei; Fu, Xueqi; Zhao, Baisong; Zhang, Pu; Fu, Xin

doi:10.1080/13880209.2019.1703756

Cited by 49 publications

(33 citation statements)

References 29 publications

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“…The present findings also revealed that ethanol inhibited PI3K/ AKT pathway, which is consistent with previous literature (Zhang et al, 2019). In fact, the activation of PI3K/AKT pathway is essential for cell resistance to oxidation and apoptosis (Arab et al, 2019;Cao et al, 2020). Our data suggest that the activation of AKT phosphorylation promoted by RUT was associated with the Nrf2 and Bcl-2 up-regulation and in turn to the down-regulation of Bax.…”

Section: Discussionsupporting

confidence: 93%

Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

Ren

Wei

et al. 2020

Front. Pharmacol.

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Background: Rutaecarpine (RUT), a major quinazolino carboline alkaloid compound from the dry unripe fruit Tetradium ruticarpum (A. Juss.) T. G. Hartley, has various pharmacological effects. The aim of this present study was to investigate the potential gastroprotective effect of rutaecarpine on ethanol-induced acute gastric mucosal injury in mice and associated molecular mechanisms, such as activating Nrf2 and Bcl-2 via PI3K/AKT signaling pathway and inhibiting NF-κB.Methods: Gastric ulcer index and histopathology was carried out to determine the efficacy of RUT in gastric ulceration, and the content of SOD, GSH in serum and CAT, MDA, MPO, TNF-α, IL-6, IL-1β in tissue were measured by kits. Besides, in order to illustrate the potential inflammatory, oxidative, and apoptotic perturbations, the mRNA levels of NF-κB p65, PI3K, AKT, Nrf2, Nqo1, HO-1, Bcl-2 and Bax were analyzed. In addition, the protein expression of NF-κB p65 and Nrf2 in cytoplasm and nucleus, AKT, p-AKT, Bcl-2 Bax and Caspase 3 were analyzed for further verification. Finally, immunofluorescence analysis was performed to further verify nuclear translocation of NF-κB p65.Results: Current data strongly demonstrated that RUT alleviated the gross gastric damage, ulcer index and the histopathology damage caused by ethanol. RUT inhibited the expression and nuclear translocation of NF-κB p65 and the expression of its downstream signals, such as TNF-α, IL-6, IL-1β and MPO. Immunofluorescence analysis also verifies the result. In the context of oxidative stress, RUT improved the antioxidant milieu by remarkably upregulating the expression Nqo1 and HO-1 with activating Nrf2, and could remarkably upregulate antioxidant SOD, GSH, CAT and downregulate levels of MDA. Additionally, RUT activate the expression of Bcl-2 and inhibited the expression of downstream signals Bax and Caspase 3 to promote gastric cellular survival. These were confirmed by RUT activation of the PI3K/AKT pathway manifested by enhanced expression of PI3K and promotion of AKT phosphorylation.Conclusion: Taken together, these results strongly demonstrated that RUT exerted a gastroprotective effect against gastric mucosal injury induced by ethanol. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis system.

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Section: Discussionsupporting

confidence: 93%

Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

Ren

Wei

et al. 2020

Front. Pharmacol.

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“…ROS inhibition can activate molecular pathways involved in cancer progression and phosphoinositide 3-kinase (PI3K)/protein kinase-B (Akt) is one of them. It has been reported that activation of PI3K/Akt axis not only promotes proliferation and metastasis of cancer cells [122][123][124][125], but also triggers chemoresistance [126][127][128][129]. Therefore, it is important to reveal the role of this molecular pathway in CP resistance of cancer cells and providing prospects for its targeting.…”

Section: Cisplatin Resistancementioning

confidence: 99%

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

et al. 2021

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The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.

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“…The activation of the Akt pathway has been shown to be a central regulator of drug resistance in cancer, arising from interactions with pro-survival pathways such as the MAPK, Notch and Wnt/β-catenin signalling pathways [114]. Inhibition of the Akt pathway has been shown to overcome resistance to cisplatin in a variety of cancer types [115][116][117][118], hence targeting the Akt signalling pathway is an attractive target for current cancer therapy studies [114]. To date, a small number of studies have investigated the effect of NNMT upon drug resistance in cancer.…”

Section: Nnmt Activates the Akt Signalling Pathwaymentioning

confidence: 99%

Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution

Parsons

Facey

2021

Biomolecules

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Nicotinamide N-methyltransferase (NNMT) has progressed from being considered merely a Phase II metabolic enzyme to one with a central role in cell function and energy metabolism. Over the last three decades, a significant body of evidence has accumulated which clearly demonstrates a central role for NNMT in cancer survival, metastasis, and drug resistance. In this review, we discuss the evidence supporting a role for NNMT in the progression of the cancer phenotype and how it achieves this by driving the activity of pro-oncogenic NAD+-consuming enzymes. We also describe how increased NNMT activity supports the Warburg effect and how it promotes oncogenic changes in gene expression. We discuss the regulation of NNMT activity in cancer cells by both post-translational modification of the enzyme and transcription factor binding to the NNMT gene, and describe for the first time three long non-coding RNAs which may play a role in the regulation of NNMT transcription. We complete the review by discussing the development of novel anti-cancer therapeutics which target NNMT and provide insight into how NNMT-based therapies may be best employed clinically.

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Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway

Abstract: Fu (2020) Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway,

Cited by 49 publications

References 29 publications

Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

Rutaecarpine Ameliorates Ethanol-Induced Gastric Mucosal Injury in Mice by Modulating Genes Related to Inflammation, Oxidative Stress and Apoptosis

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

Nicotinamide N-Methyltransferase: An Emerging Protagonist in Cancer Macro(r)evolution

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