Astragalin Reduces Hexokinase 2 through Increasing miR-125b to Inhibit the Proliferation of Hepatocellular Carcinoma Cells <i>in Vitro</i> and <i>in Vivo</i>

Li, Wei; Jiang, Hao; Zhang, Lang; Cheng, Zhuo; Deng, Xukun; Gao, Shu

doi:10.1021/acs.jafc.7b02120

Cited by 54 publications

(24 citation statements)

References 53 publications

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“…More importantly, upregulation of HK2 impaired the tumor-suppressive effect of miR-615 in OS. The same interaction between HK2 and other miRNAs, such as miR-125b and miR-143, have also been identified in human cancers (35,36). In OS, upregulation of HK2 has been reported to attenuate the inhibition of cell growth and motility induced by miR-497 (37).…”

Section: Discussionmentioning

confidence: 69%

MicroRNA‑615 functions as a tumor suppressor in osteosarcoma through the suppression of HK2

Wang

Zhang

et al. 2020

Oncol Lett

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At present, the regulatory mechanisms of various microRNAs (miRNAs/miRs) have been elucidated in human cancers including osteosarcoma (OS). This study mainly focused on the role of miR-615 in OS, which has not yet been reported. Ninety-two OS tissues and normal samples were used in this study. Human osteoblast hFOB1.19 cells and OS cell line HOS were utilized to detect the expression of miR-615. The expression of miR-615 and gene expression were assessed by RT-qPCR and western blot analysis. Transwell, MTT and luciferase reporter assays were used to investigate the regulatory mechanism of miR-615 in OS. The results revealed that miR-615 expression was reduced in OS tissues and cells, and was associated with poor clinical outcomes and prognosis in OS patients. In addition, overexpression of miR-615 restrained cell viability and metastasis in OS. Furthermore, hexokinase 2 (HK2) was confirmed as a direct target of miR-615. Upregulation of HK2 was detected in OS tissues. The upregulation of HK2 weakened the tumor-suppressive effect of miR-615 in OS. Moreover, miR-615 blocked epithelial-mesenchymal transition (EMT) and inactivated the PI3K/AKT pathway in OS. To conclude, miR-615 acts as a tumor suppressor in OS, thus miR-615 can be used as a target for OS treatment.

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Section: Discussionmentioning

confidence: 69%

MicroRNA‑615 functions as a tumor suppressor in osteosarcoma through the suppression of HK2

Wang

Zhang

et al. 2020

Oncol Lett

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“…3 ), possessing inhibitory efficacy against HKII and some specific cancer types. Astraglin was shown to reduce the activity of HKII by boosting microRNA-125b, and therefore inhibiting the proliferation of hepatocellular carcinoma (HCC) cells in vitro and in vivo [ 56 , 80 ]. The increase in expression of microRNA-125b was shown to suppress the proliferation of the HCC cells via the microRNA-125b/HKII cascade.…”

Section: Inhibition Of Hexokinase (Hk)mentioning

confidence: 99%

Inhibition of Glycolysis and Glutaminolysis: An Emerging Drug Discovery Approach to Combat Cancer

Akins

Nielson

2018

CTMC

194

139

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Cancer cells have a very different metabolism from that of normal cells from which they are derived. Their metabolism is elevated, which allows them to sustain higher proliferative rate and resist some cell death signals. This phenomenon, known as the “Warburg effect”, has become the focus of intensive efforts in the discovery of new therapeutic targets and new cancer drugs. Both glycolysis and glutaminolysis pathways are enhanced in cancer cells. While glycolysis is enhanced to satisfy the increasing energy demand of cancer cells, glutaminolysis is enhanced to provide biosynthetic precursors for cancer cells. It was recently discovered that there is a tyrosine phosphorylation of a specific isoform of pyruvate kinase, the M2 isoform, that is preferentially expressed in all cancer cells, which results in the generation of pyruvate through a unique enzymatic mechanism that is uncoupled from ATP production. Pyruvate produced through this unique enzymatic mechanism is converted primarily into lactic acid, rather than acetyl-CoA for the synthesis of citrate, which would normally then enter the citric acid cycle. Inhibition of key enzymes in glycolysis and glutaminolysis pathways with small molecules has provided a novel but emerging area of cancer research and has been proven effective in slowing the proliferation of cancer cells, with several inhibitors being in clinical trials. This review paper will cover recent advances in the development of chemotherapeutic agents against several metabolic targets for cancer therapy, including glucose transporters, hexokinase, pyruvate kinase M2, glutaminase, and isocitrate dehydrogenase.

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“…Several investigations on astragalin have explained its anticancer effect due to its promising competency to inhibit proliferation in different cancer cell lines including leukemia (HL-60) [ 15 ], hepatocellular (HepG2, Huh-7, and H22) [ 150 ], skin (HaCaT, A375P, and SK-MEL-2) [ 151 ], and lung (A549 and H1299) cancerous cells [ 145 ].…”

Section: Biological Activities Of Astragalin and Their Mechanisms mentioning

confidence: 99%

“…Moreover, AG-triggered cell death is affiliated with increased Bax : Bcl-2 ratio and enhanced cleavage of caspase-3/-9 and PARP in conjunction with blockage of PI3K/Akt, MAPK, and ERK 1/2 signaling cascades in a time- and dose-related manner [ 145 ]. In hepatocellular carcinoma cells, astragalin (AG) significantly suppressed proliferation both in vitro in HepG2 cells and in vivo in Huh-7 (nude mice) and H22 (Kunming mice) cells via mechanistically inhibiting hexokinase 2 and upregulating miR-125b expression, respectively [ 150 ].…”

Section: Biological Activities Of Astragalin and Their Mechanisms mentioning

confidence: 99%

Astragalin: A Bioactive Phytochemical with Potential Therapeutic Activities

Riaz

Rasul

Hussain

et al. 2018

Advances in Pharmacological Sciences

136

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Natural products, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovery of drugs. This review article intends to emphasize on one of the naturally occurring flavonoids, astragalin (kaempferol 3-glucoside), which is a bioactive constituent of various traditional medicinal plants such as Cuscuta chinensis. This multifaceted compound is well known for its diversified pharmacological applications such as anti-inflammatory, antioxidant, neuroprotective, cardioprotective, antiobesity, antiosteoporotic, anticancer, antiulcer, and antidiabetic properties. It carries out the aforementioned activities by the regulation and modulation of various molecular targets such as transcription factors (NF-κB, TNF-α, and TGF-β1), enzymes (iNOS, COX-2, PGE2, MMP-1, MMP-3, MIP-1α, COX-2, PGE-2, HK2, AChe, SOD, DRP-1, DDH, PLCγ1, and GPX), kinases (JNK, MAPK, Akt, ERK, SAPK, IκBα, PI3K, and PKCβ2), cell adhesion proteins (E-cadherin, vimentin PAR-2, and NCam), apoptotic and antiapoptotic proteins (Beclin-1, Bcl-2, Bax, Bcl-xL, cytochrome c, LC3A/B, caspase-3, caspase-9, procaspase-3, procaspase-8, and IgE), and inflammatory cytokines (SOCS-3, SOCS-5, IL-1β, IL-4, IL-6, IL-8, IL-13, MCP-1, CXCL-1, CXCL-2, and IFN-γ). Although researchers have reported multiple pharmacological applications of astragalin in various diseased conditions, further experimental investigations are still mandatory to fully understand its mechanism of action. It is contemplated that astragalin could be subjected to structural optimization to ameliorate its chemical accessibility, to optimize its absorption profiles, and to synthesize its more effective analogues which will ultimately lead towards potent drug candidates.

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Astragalin Reduces Hexokinase 2 through Increasing miR-125b to Inhibit the Proliferation of Hepatocellular Carcinoma Cells in Vitro and in Vivo

Cited by 54 publications

References 53 publications

MicroRNA‑615 functions as a tumor suppressor in osteosarcoma through the suppression of HK2

MicroRNA‑615 functions as a tumor suppressor in osteosarcoma through the suppression of HK2

Inhibition of Glycolysis and Glutaminolysis: An Emerging Drug Discovery Approach to Combat Cancer

Astragalin: A Bioactive Phytochemical with Potential Therapeutic Activities

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