Lipoxygenase (LOX) Pathway: A Promising Target to Combat Cancer

Vishnupriya, P.; Aparna, A.; Viswanadha, Vijaya Padma

doi:10.2174/1381612826666210101153216

Cited by 22 publications

(9 citation statements)

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“…LPCAT3 then esterified these derivatives to phosphatidylethanolamines (AA-PE and AdA-PE) [ 43 ]. Lipoxygenases (LOX) are a family of iron-containing enzymes [ 44 ], which can oxidize PUFA by phosphorylating enzyme kinase G2 (PHKG2) -dependent iron pools through the diallyl site [ 45 ]. Afterwards, AA-PE and AdA-PE catalyzed by LPCAT3 are oxidized by ALOX15 to generate LPO, leading to ferroptosis [ 46 ].…”

Section: Ferroptosismentioning

confidence: 99%

Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy

Xing

Guo

et al. 2023

Cell Death Discov.

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Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer.

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Section: Ferroptosismentioning

confidence: 99%

Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy

Xing

Guo

et al. 2023

Cell Death Discov.

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“…LOX genes are upregulated in multiple cancers, particularly 5-LOX, which enhances the proliferation rate and invasive capacity of tumor cells and induce stronger anti-apoptotic signals ( Mahboubi-Rabbani and Zarghi, 2021 ). Both leukotriene receptor antagonists and 5-LOX inhibitors are already in clinical trials of several diseases ( Vishnupriya et al, 2021 ).…”

Section: Lipid Metabolismmentioning

confidence: 99%

The role of metabolic reprogramming in pancreatic cancer chemoresistance

Liu

2023

Front. Pharmacol.

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Pancreatic cancer is characterized by hidden onset, high malignancy, and early metastasis. Although a few cases meet the surgical indications, chemotherapy remains the primary treatment, and the resulting chemoresistance has become an urgent clinical problem that needs to be solved. In recent years, the importance of metabolic reprogramming as one of the hallmarks of cancers in tumorigenesis has been validated. Metabolic reprogramming involves glucose, lipid, and amino acid metabolism and interacts with oncogenes to affect the expression of key enzymes and signaling pathways, modifying the tumor microenvironment and contributing to the occurrence of drug tolerance. Meanwhile, the mitochondria are hubs of the three major nutrients and energy metabolisms, which are also involved in the development of drug resistance. In this review, we summarized the characteristic changes in metabolism during the progression of pancreatic cancer and their impact on chemoresistance, outlined the role of the mitochondria, and summarized current studies on metabolic inhibitors.

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“…Interestingly, this population also expressed CALB1 which is associated with the kidney duct (28). Lastly, cluster #8 (i.e., PP-4) was enriched in in ammatory and EMT-inducing markers, often associated with pancreatitis and pancreatic ductal adenocarcinoma, such as LTB (29), IL32 (30), and AREG (31). Cluster #9 was assigned to endocrine cells for their high expression levels of CHGA, INS, NEUROG3, and NKX2.2 (32) (~ 8.7%, cluster #9.…”

Section: Pp Differentiation In 3d Led To Diverse Cell Populationsmentioning

confidence: 99%

Photo-click hydrogels for 3D in situ differentiation of pancreatic progenitors from induced pluripotent stem cells

Arkenberg

Ueda

Hashino

et al. 2023

Preprint

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Background Induced pluripotent stem cells (iPSC) can be differentiated to cells in all three germ layers, as well as cells in the extraembryonic tissues. Efforts in iPSC differentiation into pancreatic progenitors in vitro have largely been focused on optimizing soluble growth cues in conventional two-dimensional (2D) culture, whereas the impact of three-dimensional (3D) matrix properties on the morphogenesis of iPSC remains elusive.Methods In this work, we employ gelatin-based thiol-norbornene photo-click hydrogels for in situ 3D differentiation of human iPSCs into pancreatic progenitors (PP). Molecular analysis and single cell RNA-sequencing were utilized to elucidate on the distinct identities of subpopulations within the 2D and 3D differentiated cells.Results We found that, while established soluble cues led to predominately PP cells in 2D culture, differentiation of iPSCs using the same soluble factors led to prominent branching morphogenesis, ductal network formation, and generation of diverse endoderm populations. Through single-cell RNA-sequencing, we found that 3D differentiation resulted in enrichments of pan-endodermal cells and ductal cells. We further noted the emergence of a group of extraembryonic cells in 3D, which was absent in 2D differentiation. The unexpected emergence of extraembryonic cells in 3D was found to be associated with enrichment of Wnt and BMP signaling pathways, which may have contributed to the emergence of diverse cell populations. The expressions of PP signature genes PDX1 and NKX6.1 were restored through inhibition of Wnt signaling at the beginning of the posterior foregut stage.Conclusions To our knowledge, this work established the first 3D hydrogel system for in situ differentiation of human iPSCs into PPs. Ongoing work focuses on enhancing pancreatic differentiation efficiency through modulating physicochemical properties of the iPSC-laden matrices.

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Lipoxygenase (LOX) Pathway: A Promising Target to Combat Cancer

Cited by 22 publications

References 0 publications

Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy

Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy

The role of metabolic reprogramming in pancreatic cancer chemoresistance

Photo-click hydrogels for 3D in situ differentiation of pancreatic progenitors from induced pluripotent stem cells

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