Baicalein inhibits breast cancer growth via activating a novel isoform of the long noncoding RNA PAX8‐AS1‐N

Yu, Xiaolan; Cao, Yong; Tang, Li; Yang, Yuting; Chen, Feng; Xia, Jianguo

doi:10.1002/jcb.26881

Cited by 40 publications

(23 citation statements)

References 59 publications

(125 reference statements)

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“…An up-regulation in NKILA expression by IDET may suppress IκB phosphorylation and NF-κB activation. Similar to these observations, the anti-invasive activities of TGF-β 47 and anti-carcinogenic activities of baicalein 48 are mediated through NKILA.…”

Section: Discussionsupporting

confidence: 70%

Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer

Verma

Rai

Awasthee

et al. 2019

Sci Rep

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The sesquiterpene lactones, Isodeoxyelephantopin (IDET) and Deoxyelephantopin (DET) are known to exhibit activities against some cancer types. The activities of these lactones against breast cancer and the molecular bases is not known. We examined the efficacy of lactones in breast cancer preclinical model. Although both lactones exhibited drug like properties, IDET was relatively effective in comparison to DET. IDET suppressed the proliferation of both invasive and non-invasive breast cancer cell lines. IDET also suppressed the colony formation and migration of breast cancer cells. The assays for Acridine Orange (AO)/Propidium Iodide (PI) staining, cell cycle distribution, phosphatidylserine externalization and DNA laddering suggested the apoptosis inducing potential of IDET. The treatment with IDET also induced an accumulation of cells in the sub-G1 and G2/M phases. The exposure of breast cancer cells to the lactone was associated with a depolarization in mitochondrial membrane potential, and cleavage of caspase and PARP. The lactone induced reactive oxygen species (ROS) generation in breast cancer cells. Further, the use of N-acetyl cysteine (NAC) suppressed IDET induced ROS generation and apoptosis. The NF-κB-p65 nuclear translocation induced by okadaic acid (OA) was suppressed by the sesquiterpene. IDET also suppressed the expression of NF-κB regulated tumorigenic proteins, and induced the expression of proapoptotic gene (Bax) in cancer cells. While the expression of oncogenic lncRNAs was suppressed, the tumor suppressor lncRNAs were induced by the sesquiterpene. Collectively, the modulation of multiple cell signaling molecules by IDET may contribute to its activities in breast cancer cells.

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Section: Discussionsupporting

confidence: 70%

Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer

Verma

Rai

Awasthee

et al. 2019

Sci Rep

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“…Compared with small molecule chemical drugs, natural products have higher therapeutic safety. They also could affect the expression level of lncRNAs, which is crucial for tumor progression (50)(51)(52)(53). In this research, we confirmed that fucoidan could effectively inhibit the progression of HCC.…”

Section: Introductionsupporting

confidence: 68%

Fucoidan Inhibits the Progression of Hepatocellular Carcinoma via Causing lncRNA LINC00261 Overexpression

Wei

Chen

et al. 2021

Front. Oncol.

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Hepatocellular carcinoma (HCC) as a main type of primary liver cancers has become one of the most deadly tumors because of its high morbidity and poor prognosis. Fucoidan is a family of natural, heparin-like sulfated polysaccharides extracted from brown algae. It is not only a widely used dietary supplement, but also participates in many biological activities, such as anti-oxidation, anti-inflammation and anti-tumor. However, the mechanism of fucoidan induced inhibition of HCC is elusive. In our study, we demonstrated that fucoidan contributes to inhibiting cell proliferation in vivo and in vitro, restraining cell motility and invasion and inducing cell cycle arrest and apoptosis. According to High-Throughput sequencing of long-non-coding RNA (lncRNA) in MHCC-97H cells treated with 0.5 mg/mL fucoidan, we found that 56 and 49 lncRNAs were correspondingly up- and down-regulated. LINC00261, which was related to the progression of tumor, was highly expressed in fucoidan treated MHCC-97H cells. Moreover, knocking down LINC00261 promoted cell proliferation by promoting the expression level of miR-522-3p, which further decreased the expression level of downstream SFRP2. Taken together, our results verified that fucoidan effectively inhibits the progression of HCC via causing lncRNA LINC00261 overexpression.

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“…4 Baicalein has important pharmacological activities, such as anti-tumorous, anti-inflammatory, antiviral and antioxidative effects. 5 Issued reports have found the inhibitory effects of baicalein on various human cancers, including non-small cell lung cancer, 6 hepatocellular carcinoma, 7 breast cancer, 8 thyroid cancer, 9 and so on. Regarding the functional mechanisms of anticancer baicalein, it is mainly because of its inhibition on cell cycle progression by regulating cyclins, promotion of apoptosis by activating caspase-3/9, and the activity repression of mitogen-activated protein kinase (MAPK), protein kinase B (AKT) or mammalian target of rapamycin (mTOR).…”

Section: Introductionmentioning

confidence: 99%

Baicalein Represses Cervical Cancer Cell Growth, Cell Cycle Progression and Promotes Apoptosis via Blocking AKT/mTOR Pathway by the Regulation of circHIAT1/miR-19a-3p Axis

Hu¹,

Wang²,

Liu³

et al. 2021

OTT

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Background: Baicalein has a significant anti-cancerous function in the treatment of cervical cancer (CC). Its functional mechanism regarding circular RNA (circRNA) hippocampus abundant transcript 1 (circHIAT1) and microRNA-19a-3p (miR-19a-3p) was explored in this research. Methods: CC cell viability and colony formation were determined using Cell Counting Kit-8 (CCK-8) and colony formation assay. Cell cycle progression and apoptosis were analyzed via flow cytometry. Protein markers of cell cycle, apoptosis and protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway were detected by Western blot. CircHIAT1 and miR-19a-3p levels were assayed through the quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between circHIAT1 and miR-19a-3p was validated by dual-luciferase reporter and RNA pull-down assays. In vivo experiment was performed by xenograft model. Results: CC cell growth and cell cycle progression were repressed while apoptosis was enhanced by baicalein. MiR-19a-3p was downregulated in baicalein-treated CC cells and miR-19a-3p overexpression lightened the baicalein-induced CC progression inhibition. Moreover, circHIAT1 was found to be a sponge of miR-19a-3p in CC cells. Baicaleininduced cell growth inhibition, cell cycle arrest and apoptosis promotion were neutralized by knockdown of circHIAT1 via targeting miR-19a-3p. Baicalein acted on the circHIAT1/miR-19a-3p to inactivate AKT/mTOR pathway. Baicalein also reduced CC tumor growth in vivo via regulating the levels of circHIAT1 and miR-19a-3p. Conclusion: These findings demonstrated that the inhibitory function of baicalein in CC progression was dependent on the repression of AKT/mTOR pathway by upregulating circHIAT1 to sponge miR-19a-3p, showing a specific mechanism for baicalein in CC.

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Baicalein inhibits breast cancer growth via activating a novel isoform of the long noncoding RNA PAX8‐AS1‐N

Cited by 40 publications

References 59 publications

Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer

Isodeoxyelephantopin, a Sesquiterpene Lactone Induces ROS Generation, Suppresses NF-κB Activation, Modulates LncRNA Expression and Exhibit Activities Against Breast Cancer

Fucoidan Inhibits the Progression of Hepatocellular Carcinoma via Causing lncRNA LINC00261 Overexpression

Baicalein Represses Cervical Cancer Cell Growth, Cell Cycle Progression and Promotes Apoptosis via Blocking AKT/mTOR Pathway by the Regulation of circHIAT1/miR-19a-3p Axis

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