Kaempferol impairs aerobic glycolysis against melanoma metastasis via inhibiting the mitochondrial binding of HK2 and VDAC1

Zheng, Xiuqin; Yang, Gejun; Liu, Yang; Zou, Jueyao; Zhao, Han; Yin, Gang; Wu, Yuanyuan; Li, Xiaoman; Wei, Zhonghong; Yu, Suyun; Zhao, Yang; Wang, Aiyun; Chen, Wenxing; Li, Yin

doi:10.1016/j.ejphar.2022.175226

Cited by 14 publications

(11 citation statements)

References 41 publications

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“… 33 Combination of HK2 with VDAC1 triggers the opening of the channel, releases mitochondrial ATP, and promotes the coupling of glycolysis and mitochondrial oxidative phosphorylation, greatly increasing ATP production to meet the energy needs of cells, and plays an important role in maintaining a constant source of energy for tumor cell proliferation. 34 Research has shown that HK2 is highly expressed in FLT3-ITD AML cells, which is consistent with the high level of glycolysis in this leukemia cell. In addition, the binding of HK2-VDAC1 also plays another important role in inhibiting apoptosis.…”

Section: Discussionsupporting

confidence: 68%

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia

Peng,

Fan,

Luo

et al. 2024

Technol Cancer Res Treat

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Background Acute myeloid leukemia (AML) with Fms-like tyrosine kinase 3 gene internal tandem duplication (FLT3-ITD) mutations has a poor prognosis. The combination of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) has a synergistic killing effect on leukemia cells with FLT3-ITD mutation. However, the mechanism, especially the changes of gene expression and metabolic activity remain unclear. Here we explore the transcriptome and metabolomics changes of FLT3-ITD AML cells treated with ATO/ATRA. Methods RNA-seq was used to identify differential expressed genes (DEGs), and ultra-high performance liquid chromatography-quadrupole electrostatic field orbital trap mass spectrometry (UHPLC-QE-MS) nontargeted metabolomics method was used to screen out the differential metabolites in FLT3-ITD mutant cell lines treated with ATRA and ATO. KEGG pathway database was utilized for pathway exploration and Seahorse XF24 was used to detect extracellular acidification rate (ECAR). Metabolic polymerase chain reaction (PCR) array and real-time quantitative PCR (RT-qPCR) were used to detect mRNA levels of key metabolic genes of glycolysis and fatty acid after drug treatment. Results A total of 3873 DEGs were identified and enriched in 281 Gene Ontology (GO) terms, among which 210 were related to biological processes, 43 were related to cellular components, and 28 were related to molecular functions. Besides, 1794 and 927 differential metabolites were screened in positive and negative ion mode separately, and 59 different metabolic pathways were involved, including alanine-aspartate-glutamate metabolic pathway, arginine, and proline metabolic pathway, glycerophospholipid metabolic pathways, etc. According to KEGG Pathway analysis of transcriptome combined with metabolome, glycolysis/gluconeogenesis pathway and fatty acid metabolism pathway were significantly founded enriched. ATRA + ATO may inhibit the glycolysis of FLT3-ITD AML cells by inhibiting FLT3 and its downstream AKT/HK2-VDAC1 signaling pathway. Conclusions The gene transcription profile and metabolites of FLT3-ITD mutant cells changes significantly after treatment, which might be related to the anti-FLT3-ITD AML effect. The screened DEGs, differential metabolites pathway are helpful in studying the mechanism of anti-leukemia effects and drug targets.

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Section: Discussionsupporting

confidence: 68%

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia

Peng,

Fan,

Luo

et al. 2024

Technol Cancer Res Treat

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“…Kaempferol treatment showed a role in the inhibition of the migration and invasion of A375 as well as B16F10 cells and decreased the lung metastasis of melanoma cells. In conclusion, kaempferol inhibited melanoma metastasis through stopping the aerobic glycolysis of melanoma cells, in which the binding of HK2 as well as VDAC1 on mitochondria was broken [159].…”

Section: Skin Cancermentioning

confidence: 90%

Effects and Mechanisms of Kaempferol in the Management of Cancers through Modulation of Inflammation and Signal Transduction Pathways

Almatroudi

Allemailem

Alwanian

et al. 2023

IJMS

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Cancer is the principal cause of death and its incidence is increasing continuously worldwide. Various treatment approaches are in practice to treat cancer, but these treatment strategies may be associated with severe side effects and also produce drug resistance. However, natural compounds have established their role in cancer management with minimal side effects. In this vista, kaempferol, a natural polyphenol, mainly found in vegetables and fruits, has been revealed to have many health-promoting effects. Besides its health-promoting potential, its anti-cancer potential has also been described in in vivo as well as in in vitro studies. The anti-cancer potential of kaempferol has been proven through modulation of cell signaling pathways in addition to the induction of apoptosis and cell cycle arrest in cancer cells. It leads to the activation of tumor suppressor genes, inhibition of angiogenesis, PI3K/AKT pathways, STAT3, transcription factor AP-1, Nrf2 and other cell signaling molecules. Poor bioavailability of this compound is one of the major limitations for its proper and effective disease management actions. Recently, some novel nanoparticle-based formulations have been used to overcome these limitations. The aim of this review is to provide a clear picture regarding the mechanism of action of kaempferol in different cancers through the modulation of cell signaling molecules. Besides this, strategies to improve the efficacy and synergistic effects of this compound have also been described. However, more studies are needed based on clinical trials to fully explore the therapeutic role of this compound, especially in cancer treatment.

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“…One hundred and twenty-six articles were selected for the next phase. After full-text reading, 64 articles were included in the qualitative synthesis [10,12,14,17,. The list of excluded studies and reasons for exclusion are shown in Appendix B.…”

Section: Study Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Within this context, KMP has been shown to regulate different mechanisms involved in oncogenesis and to sensitize neoplastic cells to chemotherapeutic agents [14][15][16]. Furthermore, KMP can induce mechanisms that disrupt the survival of tumor cells [14,17]. The literature exploring KMP potential in cancer treatment is extensive, but no systematic synthesis of in vitro studies elucidating the molecular mechanisms and pathways targeted by KMP is available.…”

Section: Introductionmentioning

confidence: 99%

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The Anticancer Potential of Kaempferol: A Systematic Review Based on In Vitro Studies

de Morais,

de Oliveira,

Farias Morais

et al. 2024

Cancers

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Given the heterogeneity of different malignant processes, planning cancer treatment is challenging. According to recent studies, natural products are likely to be effective in cancer prevention and treatment. Among bioactive flavonoids found in fruits and vegetables, kaempferol (KMP) is known for its anti-inflammatory, antioxidant, and anticancer properties. This systematic review aims to highlight the potential therapeutic effects of KMP on different types of solid malignant tumors. This review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Science Direct, Scopus, and Google Scholar. After the application of study criteria, 64 studies were included. In vitro experiments demonstrated that KMP exerts antitumor effects by controlling tumor cell cycle progression, proliferation, apoptosis, migration, and invasion, as well as by inhibiting angiogenesis. KMP was also able to inhibit important markers that regulate epithelial–mesenchymal transition and enhanced the sensitivity of cancer cells to traditional drugs used in chemotherapy, including cisplatin and 5-fluorouracil. This flavonoid is a promising therapeutic compound and its combination with current anticancer agents, including targeted drugs, may potentially produce more effective and predictable results.

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Kaempferol impairs aerobic glycolysis against melanoma metastasis via inhibiting the mitochondrial binding of HK2 and VDAC1

Cited by 14 publications

References 41 publications

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia

The Potential Transcriptomic and Metabolomic Mechanisms of ATO and ATRA in Treatment of FLT3-ITD Acute Myeloid Leukemia

Effects and Mechanisms of Kaempferol in the Management of Cancers through Modulation of Inflammation and Signal Transduction Pathways

The Anticancer Potential of Kaempferol: A Systematic Review Based on In Vitro Studies

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