PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β Signaling Induced by Resveratrol

Li, Yong; Yang, Yingli; Li, Xiaoping; Long, Yiwen; Zheng, Yonghua

doi:10.1177/0963689719885083

Cited by 37 publications

(39 citation statements)

References 22 publications

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“…We regulated the expression of PRMT5 in BCCs, finding that silencing the expression of it could suppress the proliferation and invasion of BCCs and promote their apoptosis. A previous study revealed that PRMT5 was highly expressed in triple-negative BC, and it believed that PRMT5 was necessary for cell proliferation, 19 and some studies about other tumors also reported that PRMT5 had certain regulatory effects on proliferation, invasion and apoptosis of tumor cells, 20,21 which was consistent with our results. The abnormality of aerobic glycolysis is considered as one of the tumor markers, and in BC, aerobic glycolysis can not only provide nutrition for cell proliferation but also help to promote cell proliferation and metastasis.…”

Section: Discussionsupporting

confidence: 91%

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

Han¹,

Wei²,

Wu³

2020

OTT

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Objective: To explore the effects of protein arginine methyltransferase 5 (PRMT5) on the biological function of breast cancer cells (BCCs) by regulating the liver X receptor α (LXRα)/NF-κBp65 pathway. Methods: A total of 80 patients with breast cancer (BC) admitted to our hospital were collected, and 80 breast cancer tissue specimens and 80 corresponding tumor-adjacent tissue specimens were sampled from them for analysis. The reverse transcription-polymerase chain reaction (RT-PCR) was employed to determine the expression of PRMT5 mRNA in the sampled tissues, and the Western blot to determine the expression of LXRα and NF-κBp65 proteins in the tissues and cells. The patients were followed up to analyze their 3-year survival rate. Stable and transient overexpression vectors and inhibition vectors were constructed and transfected into BCCs. The cell counting kit-8 (CCK8), transwell, and flow cytometry were adopted to analyze the proliferation, invasion, and apoptosis of transfected cells, on which the effects of PRMT5 on LXRα and NF-κBp65 proteins were analyzed. Results: PRMT5 was highly expressed in BC patients, and LXRα was lowly expressed in them, which had a high diagnostic value. Patients with high expression of PRMT5 showed a poor prognosis, and the expression of PRMT5 was related to the tumor size, pathological stage, differentiation, and metastatic in BC patients. Overexpressed PRMT5 enhanced the cell proliferation, invasion, and glycolysis abilities, weakened apoptosis ability, further lowered expression of LXRα and increased expression of NF-κBp65, while inhibited PRMT5 caused opposite results in those aspects. Up-regulating the expression of LXRα suppressed the proliferation, invasion, and aerobic glycolysis of BCCs and promoted their apoptosis, while inhibiting it posed opposite effects. The rescue experiment revealed that down-regulating the expression of PRMT5 could counteract the promotion of downregulation of LXRα on proliferation, invasion and glycolysis of BCCs, and the nude mouse tumorigenesis test revealed that PRMT5 induced tumor on nude mice by mediating LXRα/NF-κBp65. Conclusion: Inhibition of the PRMT5 expression can accelerate apoptosis of BCCs and weaken their proliferation, invasion, and aerobic glycolysis through the LXRα/NF-κBp65 pathway.

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Section: Discussionsupporting

confidence: 91%

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

Han¹,

Wei²,

Wu³

2020

OTT

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“…As is known, AKT substrate GSK3β is negatively modulated by AKT activity, while activated GSK3β-Ser9 (non-phosphorylated state) is reported to regulate cell cycle analysis and apoptosis [38][39][40]. In our research, we also analyzed the effects of LF-MF on the activities of GSK3β in MCF-7 and ZR-75-1 cells.…”

Section: Discussionmentioning

confidence: 89%

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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“…It has been known that resveratrol can increase the sensitivity of tumor cells to other drugs besides its anticancer effects 43 , 44 . Resveratrol is also able to reverse the drug resistance of cancer cells 48 , 49 .…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study showed that resveratrol effectively inhibited in vitro growth of ATC cells [19][20][21][22], and has preventive and therapeutic effect on the thyroid carcinogenesis induced by diethylnitrosamine (DEN), N-methyl-Nnitrosourea (MNU) and dihydroxydipropylnitrosamine (DHPN) [41]. Although resveratrol is able to enhance chemosensitivity of the cultured cancer cells [43,44], the impacts of resveratrol on docetaxel/ doxorubicin-resistant ATC cells remain unknown. It would be therefore of clinical significance if the anti-ATC effects and the conversion ability of resveratrol to docetaxel/doxorubicin-resistance can be confirmed in vivo.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol and its Nanoparticle suppress Doxorubicin/Docetaxel-resistant anaplastic Thyroid Cancer Cells in vitro and in vivo

Xiong¹,

Lin²,

Nie³

et al. 2021

Nanotheranostics

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Background: Docetaxel and doxorubicin combination has been widely used in anaplastic thyroid cancer/ATC treatment but often results in serious adverse effects and drug resistance. Resveratrol effectively inhibits ATC cell proliferation in vitro without affecting the corresponding normal cells, while its in vivo anti-ATC effects especially on the ones with docetaxel/doxorubicin-resistance have not been reported due to its low bioavailability. Nanoparticles with sustained-release and cancer-targeting features may overcome this therapeutic bottleneck. Methods: The resveratrol nanoparticles with sustained-release and IL-13Rα2-targeting capacities (Pep-1-PEG3.5k-PCL4k@Res) were prepared to improve the in vivo resveratrol bioavailability. Human THJ-16T ATC cell line was employed to establish nude mice subcutaneous transplantation model. The tumor-bearing mice were divided into four groups as Group-1, without treatment, Group-2, treated by 30 mg/kg free resveratrol, Group-3, treated by 30 mg/kg Pep-1-PEG3.5k-PCL4k@Res and Group-4, treated by 5 mg/kg docetaxel/5 mg/kg doxorubicin combination. TUNEL staining was used to detect the apoptotic cells in the tumor tissues. Docetaxel/doxorubicin resistant xenografts named as THJ-16T/R were isolated and subjected to 2D and 3D culture. The docetaxel/doxorubicin and resveratrol sensitivities of the original THJ-16T and THJ-16T/R cells were analyzed by multiple methods. Results: Docetaxel/doxorubicin and Pep-1-PEG3.5k-PCL4k@Res but not free resveratrol significantly delayed tumor growth (P < 0.01) and caused extensive apoptosis. The mice in docetaxel/doxorubicintreated group suffered from weight loss (> 10%) and 2/3 of them died within 3 times of treatment and the chemotherapy was stop to avoid further animal loss. One week after drug withdrawal, the subcutaneous tumors regrew and the tumor volume increased 55.28% within 14 days. The cells isolated from the regrowing tumors (THJ-16T/R) were successfully cultured under 2D and 3D condition and underwent drug treatments. Compared with THJ-16T, the death rate of docetaxel/doxorubicin-treated THJ-16T/R population was lower (39.3% vs 18.0%), which remained almost unchanged in resveratrol-treated group (45.3% vs 49.3%). Conclusion: Resveratrol sustained-release targeting nanoparticles effectively inhibit in vivo ATC growth. Docetaxel/doxorubicin suppresses ATC xenografts but causes obvious side effects and secondary drug resistance that can be overcome by resveratrol.

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PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β Signaling Induced by Resveratrol

Cited by 37 publications

References 22 publications

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

<p>PRMT5 Promotes Aerobic Glycolysis and Invasion of Breast Cancer Cells by Regulating the LXRα/NF-κBp65 Pathway</p>

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

Resveratrol and its Nanoparticle suppress Doxorubicin/Docetaxel-resistant anaplastic Thyroid Cancer Cells in vitro and in vivo

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