The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model

Krajnović, Tamara; Drača, Dijana; Kaluđerović, Goran N.; Dunđerović, Duško; Mirkov, Ivana; Wessjohann, Ludger A.; Maksimović‐Ivanić, Danijela; Mijatović, Sanja

doi:10.1016/j.fct.2019.04.046

Cited by 18 publications

(21 citation statements)

References 77 publications

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“…In addition, it was also confirmed that chrysin inhibited the autophagy flux of these drug-resistant cells through an mTOR-independent pathway [60,61]. Although inducing protective autophagy in diverse tumor cells, EGCG alleviated gefitinib resistance in NSCLC by inhibiting autophagy and augmenting cell death through the inhibition of ERK phosphorylation [81].…”

Section: Targeting Autophagy Regulates Mdrmentioning

confidence: 72%

Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

et al. 2021

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Autophagy, which is a conserved biological process and essential mechanism in maintaining homeostasis and metabolic balance, enables cells to degrade cytoplasmic constituents through lysosomes, recycle nutrients, and survive during starvation. Autophagy exerts an anticarcinogenic role in normal cells and inhibits the malignant transformation of cells. On the other hand, aberrations in autophagy are involved in gene derangements, cell metabolism, the process of tumor immune surveillance, invasion and metastasis, and tumor drug-resistance. Therefore, autophagy-targeted drugs may function as anti-tumor agents. Accumulating evidence suggests that flavonoids have anticarcinogenic properties, including those relating to cellular proliferation inhibition, the induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, the impairment of cell migration, invasion, tumor angiogenesis, and the reduction of multidrug resistance in tumor cells. Flavonoids, which are a group of natural polyphenolic compounds characterized by multiple targets that participate in multiple pathways, have been widely studied in different models for autophagy modulation. However, flavonoid-induced autophagy commonly interacts with other mechanisms, comprehensively influencing the anticancer effect. Accordingly, targeted autophagy may become the core mechanism of flavonoids in the treatment of tumors. This paper reviews the flavonoid-induced autophagy of tumor cells and their interaction with other mechanisms, so as to provide a comprehensive and in-depth account on how flavonoids exert tumor-suppressive effects through autophagy.

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Section: Targeting Autophagy Regulates Mdrmentioning

confidence: 72%

Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

et al. 2021

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“…Its female flowers (cones) are mainly used in beer brewing as a flavouring as well as bittering agent because of the high abundance of secondary metabolites, including bitter acids, terpenes and polyphenols (De Keukeleire et al, 2003; Cleemput et al, 2009; Kavalier et al, 2011). In addition, numerous compounds make hops a source of pharmaceuticals in modern applications, with activity against metabolic syndromes (Cleemput et al, 2009; Miranda et al, 2018), anti‐cancer (Farag & Wessjohann, 2013; Jiang, Sun, Xiang, Wei, & Li, 2018; Krajnovic et al, 2019; Krajnovic, Kaluderovic, Wessjohann, Mijatovic, & Maksimovic‐Ivanic, 2016) and phytoestrogenic properties (Possemiers et al, 2006; Stevens & Page, 2004; Wilhelm & Wessjohann, 2006). Diverse factors, such as a high degree of heterozygosity, dioecy and obligate outcrossing, a poorly understood gender‐determination system and a large genome size of 2.7 Gbp (Padgitt‐Cobb et al, 2019), contribute to the difficulty of hop breeding (Darby, 2006; Easterling et al, 2018; Neve, 1991; Zhang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Downy mildew resistance is genetically mediated by prophylactic production of phenylpropanoids in hop

Feiner

Pitra²,

Matthews³

et al. 2020

Plant Cell & Environment

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Downy mildew in hop (Humulus lupulus L.) is caused by Pseudoperonospora humuli and generates significant losses in quality and yield. To identify the biochemical processes that confer natural downy mildew resistance (DMR), a metabolome-and genomewide association study was performed. Inoculation of a high density genotyped F1 hop population (n = 192) with the obligate biotrophic oomycete P. humuli led to variation in both the levels of thousands of specialized metabolites and DMR. We observed that metabolites of almost all major phytochemical classes were induced 48 hr after inoculation. But only a small number of metabolites were found to be correlated with DMR and these were enriched with phenylpropanoids. These metabolites were also correlated with DMR when measured from the non-infected control set. A genome-wide association study revealed co-localization of the major DMR loci and the phenylpropanoid pathway markers indicating that the major contribution to resistance is mediated by these metabolites in a heritable manner. The application of three putative prophylactic phenylpropanoids led to a reduced degree of leaf infection in susceptible genotypes, confirming their protective activity either directly or as precursors of active compounds.

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“…Such as Hederagenin, it can inhibit the proliferation of cervical cancer CaSki cells and promote their apoptosis by blocking the STAT3 pathway (34) . And Isoxanthohumol can inhibit the formation of lung metastasis in B16-F10 murine melanoma model (35) . Tripterygium also exhibited signi cant inhibitory effects on many cancer cells (36) .…”

Section: Discussionmentioning

confidence: 93%

Network Pharmacology-Based Strategy for Predicting Therapy Targets of Tripterygium wilfordii on Acute Myeloid Leukemia

Fang

Liu

Chen

2020

Preprint

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Background. Acute myeloid leukemia (AML) is a common malignant tumor of the hematopoietic system. How to extend the survival time of AML patients and improve their prognosis is still a major medical problem. Chinese medicine has a long history in treating AML. Tripterygium wilfordii (TW) is a traditional Chinese medicine. With the deepening of pharmacological research of traditional Chinese medicine, triptolide, one of its active ingredients, has been proven to have a positive effect on the treatment of AML. Therefore，this study aimed on studying the potential therapeutic targets and pharmacological mechanism of TW in Acute myeloid leukemia (AML) based on network pharmacology.Methods. The active components of TW were obtained by network pharmacology through oral bioavailability, drug-likeness filtration. Comparative analysis was used to study the overlapping genes between active ingredient’s targets and AML treatment-related targets. Using STRING database to analyze interactions between overlapping genes. KEGG pathway analysis and Gene Ontology enrichment analysis were conducted in DAVID. These genes were analyzed for survival in OncoLnc database.Key findings. We screened 53 active ingredients, the results of comparative analysis showed that 8 active ingredients had an effect on AML treatment. Based on the active ingredients and overlapping genes, we constructed the Drug-Compounds-Genes-Disease Network. Survival analysis of overlapping genes indicated that some targets possess a significant influence on patients’ survival and prognosis. The enrichment analysis showed that the main pathways of targets are Toll-like receptor signaling pathway, NF-kappa B signaling pathway and HIF-1 signaling pathway.Conclusion. This study, using a network pharmacologic approach, provides another strategy that can help us to understand the mechanisms by which TW treats AML comprehensively.

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The hop-derived prenylflavonoid isoxanthohumol inhibits the formation of lung metastasis in B16-F10 murine melanoma model

Cited by 18 publications

References 77 publications

Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

Downy mildew resistance is genetically mediated by prophylactic production of phenylpropanoids in hop

Network Pharmacology-Based Strategy for Predicting Therapy Targets of Tripterygium wilfordii on Acute Myeloid Leukemia

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