Targeting of mTORC1/2 by dihydroevocarpine induces cytotoxicity in acute myeloid leukemia

Zhang, Silin; Xiong, Yunhe; Zhang, Yixian; Zhao, Hongmei

doi:10.1002/jcp.27974

Cited by 3 publications

(2 citation statements)

References 31 publications

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“…CREB binding protein (CREBBP) is an important protein for the autonomous cellular regulation of hematopoiesis, including the stem cell [ 71 ]. For example, it is known that the bone marrow microenvironment is suppressive for the active cells of the immune system, therefore promoting the leukemic clone progression [ 72 , 73 , 74 ]. Regulatory T-cells have been identified for being used by leukemic cells to evade the immune response.…”

Section: Discussionmentioning

confidence: 99%

“…Regulatory T-cells have been identified for being used by leukemic cells to evade the immune response. In addition, the protective effects of the marrow achieve protection against cytotoxic drugs, allowing the development of cell resistance that imposes the need for the development of appropriate drugs and the microenvironment [ 72 , 73 , 74 ].…”

Section: Discussionmentioning

confidence: 99%

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Dual Mechanisms of Metabolism and Gene Expression of the CCRF-CEM Leukemia Cells under Glucocorticoid Treatment

Lambrou

Karakonstantakis

Vlahopoulos

et al. 2021

IJMS

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Background: Glucocorticoids play an essential part in anti-leukemic therapies, but resistance is a crucial event for the prognosis of the disease. Glucocorticoids influence the metabolic properties of leukemic cells. The inherent plasticity of clinically evolving cancer cells justifies the characterization of drug-induced early oncogenic pathways, which represent a likely source of detrimental secondary effects. Aim: The present work aims to investigate the effect of glucocorticoids in metabolic pathways in the CCRF-CEM leukemic cells. Metabolic factors and gene expression profiles were examined in order to unravel the possible mechanisms of the CCRF-CEM leukemic cell growth dynamics. Methods: CCRF-CEM cells were used as a model. Cells were treated with prednisolone with concentrations 0–700 μM. Cell culture supernatants were used for glucose, lactic acid, LDH, Na+, K+ and Ca++ measurements. Cytotoxicity was determined with flow cytometry. Microarray analysis was performed using two different chips of 1.2 k and 4.8 k genes. Gene Ontology enrichment analysis was applied to find metabolism- and GC-related genes. Results: Higher prednisolone concentrations inhibited glucose uptake, without exhibiting any cytotoxic effects. Glucose consumption did not correlate with the total cell population, or the viable population, indicating that growth is not directly proportional to glucose consumption. Neither of the subpopulations, i.e., viable, necrotic, or apoptotic cells, contributed to this. Conclusions: Different types of leukemic cells seem to exhibit different patterns of glucose metabolism. Both resistant and sensitive CCRF-CEM cells followed the aerobic pathway of glycolysis. There is probably a rapid change in membrane permeability, causing a general shutdown towards everything that is outside the cell. This could in part also explain the observed resistance. Glucocorticoids do not enter the cell passively anymore and therefore no effects are observed. Based on our observations, ion concentrations are measurable factors both in vitro and in vivo, which makes them possible markers of glucocorticoid cytotoxic action.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dual Mechanisms of Metabolism and Gene Expression of the CCRF-CEM Leukemia Cells under Glucocorticoid Treatment

Lambrou

Karakonstantakis

Vlahopoulos

et al. 2021

IJMS

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Traditional Chinese medicine Euodiae Fructus: botany, traditional use, phytochemistry, pharmacology, toxicity and quality control

Xiao¹,

Xu²,

Chen³

et al. 2023

Nat. Prod. Bioprospect.

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Euodiae Fructus, referred to as “Wuzhuyu” in Chinese, has been used as local and traditional herbal medicines in many regions, especially in China, Japan and Korea, for the treatment of gastrointestinal disorders, headache, emesis, aphtha, dermatophytosis, dysentery, etc. Substantial investigations into their chemical and pharmacological properties have been performed. Recently, interest in this plant has been focused on the different structural types of alkaloids like evodiamine, rutaecarpine, dehydroevodiamine and 1-methyl-2-undecyl-4(1H)-quinolone, which exhibit a wide range of pharmacological activities in preclinical models, such as anticancer, antibacterial, anti-inflammatory, anti-cardiovascular disease, etc. This review summarizes the up-to-date and comprehensive information concerning the botany, traditional uses, phytochemistry, pharmacology of Euodiae Fructus together with the toxicology and quality control, and discusses the possible direction and scope for future research on this plant.

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Traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the fruit of Tetradium ruticarpum: A review

Wang

2020

Journal of Ethnopharmacology

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Targeting of mTORC1/2 by dihydroevocarpine induces cytotoxicity in acute myeloid leukemia

Cited by 3 publications

References 31 publications

Dual Mechanisms of Metabolism and Gene Expression of the CCRF-CEM Leukemia Cells under Glucocorticoid Treatment

Dual Mechanisms of Metabolism and Gene Expression of the CCRF-CEM Leukemia Cells under Glucocorticoid Treatment

Traditional Chinese medicine Euodiae Fructus: botany, traditional use, phytochemistry, pharmacology, toxicity and quality control

Traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the fruit of Tetradium ruticarpum: A review

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