Downregulation of Cyclin B1 mediates nagilactone E-induced G2 phase cell cycle arrest in non-small cell lung cancer cells

Zhang, Le‐Le; Su, Min‐Xia; Jiang, Xiaoming; Chen, Xiuping; Wang, Ying; Li, Ao; Lin, Ligen; Lu, Jin‐Jian

doi:10.1016/j.ejphar.2018.04.020

Cited by 30 publications

(21 citation statements)

References 40 publications

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“…LF-MFs were shown to induce cell cycle arrest at the G0-G1 phase or G2-M phase [10,26], which might be caused by different exposure conditions. It is well known that Cyclin D1 is a key protein regulating the G1 phase [27], whereas the inhibition of Cyclin B1 function results in a G2-M phase arrest [28]. In this study, we found that with continuous exposure to 200 Hz-1 mT LF-MF, the cells in the G2-M phase increased, which is associated with the downregulation of Cyclin B1.…”

Section: Discussionsupporting

confidence: 48%

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Wang

Lin

2020

IJMS

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Breast cancer is a common malignancy threatening women's health around the world. Despite improved treatments for different subtypes of breast tumors that have been put forward, there still exists a poor therapeutic response and prognosis. Magnetic fields, as a non-invasive therapy, have shown anti-tumor effects in vitro and in vivo; however, the detailed mechanisms involved are still not clear. In this study, we found that in exposure to low-frequency magnetic fields (LF-MFs) with an intensity of 1 mT and frequencies of 50, 125, 200, and 275 Hz, separately, the proliferation of breast cancer cells was inhibited and LF-MF with 200 Hz reached the optimum inhibition effect, on exposure time-dependently. Notably, we found that exposure to LF-MF led to MCF-7 and ZR-75-1 cell apoptosis and cell cycle arrest. Moreover, we also discovered that LF-MF effectively increased the level of reactive oxygen species (ROS), suppressed the PI3K/AKT signaling pathway, and activated glycogen synthase kinase-3β (GSK-3β). We demonstrated that the GSK3β activity contributed to LF-MF-induced cell proliferation inhibition and apoptosis, while the underlying mechanism was associated with the inhibition of PI3K/AKT through increasing the intracellular ROS accumulation. These results indicate that LF-MF with a specific frequency may be an attractive therapy to treat breast cancers.Int. J. Mol. Sci. 2020, 21, 2952 2 of 14 processes [9]. Further research has found that low-frequency magnetic fields (LF-MFs), namely, those with a frequency below 300 Hz, possess a variety of effects such as the regulation of immunity [10] and inflammation [11], suppression of angiogenesis [12], contribution to differentiation [13], and induced apoptosis [14]. Although many biological effects of magnetic fields have been reported, the mechanisms involved still remain unclear.Reactive oxygen species (ROS), including superoxide and hydrogen peroxide, are one of the main causes of tumors and play an important role in the process of tumor progression, metastasis and apoptosis [15]. Low-frequency magnetic fields have been demonstrated to significantly increase the intracellular ROS levels in many kinds of cells [16]. The PI3K/AKT pathway is a pivotal signaling pathway, which is closely related to the regulation of cell survival, apoptosis, migration and proliferation [17]. The relationship between ROS and the PI3K/AKT pathway in apoptosis regulation has been confirmed in several studies [18,19]. Glycogen synthase kinase-3β (GSK-3β) is an effector of PI3K/AKT, and is a kind of serine / threonine protein kinase, whose biological function is far beyond the glucose synthesis-regulating enzyme it was initially considered. GSK-3β can phosphorylate many substrates, including metabolism and signal protein, transcription factors of cell structural protein, etc., playing an important role in the process of tumor occurrence and development [20,21]. Baihuan Feng et al. reported that exposure to 50 Hz-0.4 mT MF affected mitochondrial permeability by the ROS-regulating phosphoryla...

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Section: Discussionsupporting

confidence: 48%

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Wang

Lin

2020

IJMS

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“…Notably, multivariate analysis has identified CCNB1 expression as a prognostic factor for patients with NScLc (21,22). Functionally, ccNB1 exerts oncogenic actions and is implicated in the control of multiple cancer-related behaviors of NScLc cells (23)(24)(25)(26). In the present study, it was revealed that miR-718 directly targets CCNB1 mRNA and decreases ccNB1 expression in NScLc, thereby inhibiting cell proliferation, migration and invasion, and increasing apoptosis in vitro and suppressing tumor growth in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Among these candidates, CCNB1 (Fig. 3A) was selected for further study since this gene has been reported to have crucial roles in NScLc tumorigenesis and tumor development (20)(21)(22)(23)(24)(25)(26). To corroborate this target, the luciferase reporter assay was performed to determine whether miR-718 is able to directly interact with the 3'-UTR of CCNB1 mRNA in NScLc cells.…”

Section: Ccnb1 Is a Direct Target Of Mir-718 In Nsclc Cellsmentioning

confidence: 99%

MicroRNA‑718 serves a tumor‑suppressive role in�non‑small�cell lung cancer by directly targeting CCNB1

et al. 2019

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MicroRNA-718 (miR-718) serves crucial roles in tumorigenesis and in the progression of a number of cancers. However, the expression profile, specific functions and mechanisms of action of miR-718 in non-small cell lung cancer (NScLc) are still elusive. The aims of the present study were to quantify the expression of miR-718, determine its biological roles and elucidate the molecular mechanisms responsible for its activities in NScLc cells. Reverse transcription-quantitative PcR was carried out to assess miR-718 expression in NScLc tissue samples and cell lines. The cell counting Kit-8 assay, flow cytometry, cell migration and invasion assays, and a tumor xenograft experiment were performed to evaluate the effects of miR-718 overexpression on the malignant biological behaviors of NScLc cells. miR-718 expression was demonstrated to be significantly decreased in NSCLC tissue samples and cell lines. This reduced expression was significantly associated with tumor, node, metastasis stage, tumor size, lymph node metastasis and poor overall survival among patients with NScLc. Exogenous miR-718 expression suppressed NScLc cell proliferation, migration and invasion, and promoted apoptosis in vitro; whereas it hindered tumor growth in vivo. Experiments to elucidate the mechanisms involved revealed that miR-718 functions by directly targeting cyclin B1 (CCNB1) mRNA. CCNB1 expression was found to be upregulated in NScLc and inversely correlated with miR-718 levels. CCNB1 depletion had effects similar to those of miR-718 overexpression in NScLc cells. Furthermore, restoration of CCNB1 expression attenuated the tumor-suppressive effects of miR-718 overexpression in NScLc cells. These results indicated that miR-718 suppressed NScLc progression in vitro and in vivo by directly targeting CCNB1 mRNA, which may indicate a potential target for the diagnosis and treatment of this fatal disease.

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“…14 Similarly, Zhang et al verified that treatment with nagilactone E downregulated the expression of cyclinB1, induced cell cycle arrest at the G2 phase, and suppressed proliferation in non-small cell lung cancer cells. 15 Kedinger et al demonstrated that silencing of cyclinB1 through the use of small interfering RNAs (siRNAs) blocked the cell cycle and suppressed the proliferation of melanoma cells. Furthermore, siRNAs against cyclinB1 significantly inhibited the growth and lung metastases of subcutaneous tumors.…”

Section: Discussionmentioning

confidence: 99%

<p>Inhibition of cyclinB1 Suppressed the Proliferation, Invasion, and Epithelial Mesenchymal Transition of Hepatocellular Carcinoma Cells and Enhanced the Sensitivity to TRAIL-Induced Apoptosis</p>

Lv¹,

Ning²,

Li³

et al. 2020

OTT

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Background: CyclinB1 is highly expressed in various tumor tissues and plays an important role in tumor progression. However, its role in hepatocellular carcinoma (HCC) remains unclear. Therefore, the aim of this study was to explore the role of cyclinB1 in the development and progression of HCC. Methods: The expression of cyclinB1 was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database, and detected in HCC tissues and HCC cell lines through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. CyclinB1-short hairpin RNA (Sh-cyclinB1) was transfected into HCC cells to knockdown cyclinB1, and the effect of cyclinB1 knockdown on HCC was examined via the MTT assay, colony formation assay, wound healing assay, scratch assay, cell cycle analysis in vitro, and xenograft model in nude mice. In addition, the role of cyclinB1 on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis was measured using flow cytometry and Western blotting. Results: The GEPIA database analysis showed that cyclinB1 was highly expressed in HCC tissues. The results of qRT-PCR and Western blotting proved that the expression of cyclinB1 was significantly increased in HCC tissues and cell lines. The data of the MTT assay, colony formation assay, and cell cycle analysis indicated that cyclinB1 knockdown inhibited the proliferation of HCC cells. In addition, cell migration, invasion, and epithelial mesenchymal transition were also impaired by cyclinB1 knockdown. Furthermore, the xenograft model in nude mice demonstrated that inhibition of cyclinB1 suppressed tumor growth and metastasis in vivo. Finally, the results of flow cytometry and Western blotting indicated that inhibition of cyclinB1 enhanced the sensitivity of HCC cells to TRAIL-induced apoptosis. Conclusion: Overall, these data provide reasonable evidence that cyclinB1 may serve as a proto-oncogene during the progression of HCC.

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Downregulation of Cyclin B1 mediates nagilactone E-induced G2 phase cell cycle arrest in non-small cell lung cancer cells

Cited by 30 publications

References 40 publications

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

MicroRNA‑718 serves a tumor‑suppressive role in�non‑small�cell lung cancer by directly targeting CCNB1

<p>Inhibition of cyclinB1 Suppressed the Proliferation, Invasion, and Epithelial Mesenchymal Transition of Hepatocellular Carcinoma Cells and Enhanced the Sensitivity to TRAIL-Induced Apoptosis</p>

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