Isorhamnetin inhibited the proliferation and metastasis of androgen-independent prostate cancer cells by targeting the mitochondrion-dependent intrinsic apoptotic and PI3K/Akt/mTOR pathway

Cai, Fang; Zhang, Yanmei; Li, Jianwei; Huang, Sihuai; Gao, Ruilin

doi:10.1042/bsr20192826

Cited by 45 publications

(28 citation statements)

References 34 publications

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“…Western blot assay was performed as previously reported [25] with slight modifications. After incubation, the MDSCs isolated from difference group were washed three times with ice-cold PBS and suspended in RIPA lysis buffer for total cell protein extraction.…”

Section: Western Blotmentioning

confidence: 99%

Ganoderma lucidum polysaccharide (GLP) enhances antitumor immune response by regulating differentiation and inhibition of MDSCs via a CARD9-NF-κB-IDO pathway

Wang

Fan

2020

Bioscience Reports

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A homogeneous polysaccharide (GLP), with an average molecular weight of 4.44 × 104 Da, was isolated and purified from the fruiting bodies of Ganoderma lucidum. In this work, we examined the antitumor activities of GLP using a mouse Lewis lung cancer (LLC) model and explored possible molecular pathways involved in its immunomodulatory mechanism on tumor–host interaction. GLP administration (25 and 100 mg/kg) significantly inhibited tumor growth, as evidenced by the decreased tumor volume and tumor weight, as well as histological features of tumor tissues with concomitant down-regulation of proliferating cell nuclear antigen (PCNA) proliferative marker. Less myeloid-derived suppressor cells (MDSCs) were accumulated in both spleen and tumor tissues from GLP-treated mice. In contrast, the percentage of CD4+ and CD8+ T cells together with the production of Th1-type cytokines (IFN-γ and IL-12) was increased in the spleen of LLC-bearing mice following GLP administration. Furthermore, GLP administration reversed the attenuated expression of CARD9, p-Syk and p-p65, and increased indoleamine 2,3-dioxygenase (IDO) protein expression in MDSCs of LLC-bearing mice. Collectively, our data demonstrated the first time that GLP induced the differentiation of MDSCs and inhibited the accumulation of MDSCs via CARD9-NF-κB-IDO pathway, thus prevented lung cancer development.

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Section: Western Blotmentioning

confidence: 99%

Ganoderma lucidum polysaccharide (GLP) enhances antitumor immune response by regulating differentiation and inhibition of MDSCs via a CARD9-NF-κB-IDO pathway

Wang

Fan

2020

Bioscience Reports

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“…Prostate cancer, as one most prevalent urinary malignancy of the male, ranked the second place in the cause of cancer death among aged men all over the world, trailing only lung cancer [ 1 , 2 ]. Although its incidence remains relatively high in western countries, there is a sharp rise in China for the aging Chinese population over the past decade, which has caught China’s healthcare attention [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway

Luo

et al. 2021

Bioengineered

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In this study, we examined the antitumor effects of Puerarin (PEU) on androgen-independent (DU145 and PC-3) and androgen-dependent (LNCaP) prostate cancer cells, and explored its potential mechanisms. Supplement with PEU (2.5 μM, 5 μM, and 10 μM) exhibited a marked inhibitory effect against the growth of DU145 and PC-3 cells, especially beyond 24 h, whereas there is only slight growth inhibitory effect on LNCaP cells at the high concentration of 10 μM at 72 h. This loss of cell viability in DU145 and PC-3 cells by PEU was mediated by the induction of apoptosis via up-regulation of Bax and cleaved-caspase-3, but downregulation of Bcl-2. Moreover, more intracellular ROS and LDH production were observed in DU145 and PC-3 cells upon PEU treatment. Meanwhile, the amount of pro-inflammatory cytokines (IL-1β and IL-6) was increased, but the content of anti-inflammatory cytokines IL-10 was attenuated. Additionally, PEU pretreatment resulted in an increase of Keap1 protein expression, and a decline of Nrf2, HO-1 and NQO1 protein expression in DU145 and PC3 cells. The present findings indicated that PEU exerted its antitumor activities toward androgen-independent prostate cancer cells via inactivation of Keap1/ NrF2/ARE signaling pathway.

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“…Isorhamnetin is a representative avonoid compound that exhibits antitumor activity primarily by inhibiting tumor cell proliferation, inducing apoptosis, and inhibiting signal transduction. For instance, Cai et al reported that isorhamnetin inhibits the proliferation and metastasis of androgen-independent prostate cancer cells by targeting the endogenous apoptotic pathway and selectively inhibiting PI3K/Akt/mTOR signaling [40].…”

Section: Discussionmentioning

confidence: 99%

Analysis and verification of the molecular mechanism of Evodia in the treatment of nasopharyngeal carcinoma using network pharmacology and molecular docking

Yang

et al. 2022

Preprint

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Background: Nasopharyngeal carcinoma (NPC) is a neoplasm of the head and neck, with the highest incidence and mortality rates occurring in East and Southeast Asia. Evodia rutaecarpa is a tree that is native to Korea and China, and its fruit (hereafter referred to as Evodia) exhibits remarkable antitumor properties. However, little is known about its mechanism of action in NPC. In this study, we employed network pharmacology to identify targets of the active Evodia compounds in nasopharyngeal carcinoma and generate an interaction network.Methods: The active ingredients of Evodia and the targets for nasopharyngeal carcinoma were obtained from multiple databases, and an interaction network was constructed via the Cytoscape and STRING databases. The key biological processes and signaling pathways were predicted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Molecular docking technology was used to identify the affinity and activity of target genes, while The Cancer Genome Atlas and Human Protein Atlas databases were used to analyze differential expression. Cell Counting Kit (CCK)-8 and Annexin V-FITC/PI dual fluorescence staining were used for experimental verification.Results: Active Evodia compounds included quercetin, isorhamnetin, and evodiamine, and important nasopharyngeal carcinoma targets included MAPK14, AKT1, RELA, MAPK1, JUN, and p53, whose content in the lipid and atherosclerosis signaling pathways was also high. Additionally, we verified the high affinity and activity of the active compounds through molecular docking, and the target proteins were verified using immunohistochemistry and differential expression analyses. Furthermore, Cell Counting Kit-8 assays and Annexin V-FITC/propidium iodide dual-fluorescence staining verified that isorhamnetin inhibited the proliferation of nasopharyngeal carcinoma cells and induced apoptosis, respectively.Conclusion: These results elucidated the molecular mechanism of Evodia and demonstrated its ability to alter the proliferation and apoptosis of nasopharyngeal carcinoma cells through multiple targets and pathways, thereby providing evidence for its clinical application.

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Isorhamnetin inhibited the proliferation and metastasis of androgen-independent prostate cancer cells by targeting the mitochondrion-dependent intrinsic apoptotic and PI3K/Akt/mTOR pathway

Cited by 45 publications

References 34 publications

Ganoderma lucidum polysaccharide (GLP) enhances antitumor immune response by regulating differentiation and inhibition of MDSCs via a CARD9-NF-κB-IDO pathway

Ganoderma lucidum polysaccharide (GLP) enhances antitumor immune response by regulating differentiation and inhibition of MDSCs via a CARD9-NF-κB-IDO pathway

Puerarin induces apoptosis in prostate cancer cells via inactivation of the Keap1/Nrf2/ARE signaling pathway

Analysis and verification of the molecular mechanism of Evodia in the treatment of nasopharyngeal carcinoma using network pharmacology and molecular docking

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