Lycorine inhibits melanoma A375 cell growth and metastasis through the inactivation of the PI3K/AKT signaling pathway

Malignant melanoma, one of the most aggressive skin cancers, has a very high mortality rate. Currently, the number of drugs to treat melanoma is low. Although new immunotherapeutic approaches based on the use of antibodies against immune checkpoints have shown long term responses, it is urgent to develop novel anti-melanoma drugs with a high efficiency and a low toxicity in a large number of patients. Lycorine, a natural product, has been reported to exert antitumor effects on some cancers. However, the impact of lycorine on melanoma cells is still unknown. Using the CCK8 assay, we found that lycorine can suppress the proliferation of melanoma A375 cells in a dose-time-dependent manner. Moreover, a transwell assay showed that lycorine inhibited the migration and invasion of A375 cells significantly. Further, lycorine treatment could induce the apoptosis of the A375 cells. Biochemical analyses showed that the expression level of the anti-apoptosis Bcl-2 protein decreased, while the expression of the pro-apoptosis protein Bax and active caspase-3 increased after lycorine treatment. Finally, using western blot assay, we found that the antitumor effects of lycorine on A375 cells might be through the inactivation of the PI3K/Akt signaling pathway. Based on these observations, we suggest that lycorine may be an interesting candidate for further studies on its ability to represent a novel antitumor drug for human melanoma treatment in the future.

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Effects of Rhizopus Nigricans Exopolysaccharide on Proliferation, Apoptosis, and Migration of Breast Cancer MCF-7 Cells and Akt Signaling Pathway

International Journal of Polymer Science ◽

10.1155/2021/5621984 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Aizhai Xiang ◽

Chen Ling ◽

Wei Zhang ◽

Honggang Chen

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Akt Signaling ◽

Migration And Invasion ◽

Dependent Manner ◽

Akt Signaling Pathway ◽

Rhizopus Nigricans ◽

And Migration ◽

The Impact ◽

Mcf 7

Objective. To study the effect of Rhizopus nigricans exopolysaccharide EPS1-1 on the proliferation, apoptosis, and migration of breast cancer MCF-7 cells. Methods. Human breast cancer MCF-7 cells were cultured in vitro and treated with different concentrations of EPS1-1. The effect of EPS1-1 on cell proliferation was tested by the CCK-8 experiment, and the effect of EPS1-1 on cell apoptosis was determined by flow cytometry. And the scratch test was used to detect the impact of EPS1-1 on cell migration. Western blot then was used to measure the expression changes of related proteins in the Akt signaling pathway. Results. Compared with the control group, treatment with EPS1-1 significantly reduced the proliferation, migration, and invasion ability of MCF-7 cells and promoted the apoptosis of MCF-7 cells in a dose-dependent manner. In terms of the underlying mechanism, EPS1-1 can significantly inhibit the phosphorylation of Akt at threonine 308 and serine 473 and cause the expression changes of downstream proliferation-related genes CCND1 and p21, apoptosis-related genes Bcl-2 and Bax, and migration-related genes Vimentin and E-cadherin in terms of their protein levels. Conclusion. EPS1-1 can inhibit the proliferation, migration, and invasion of breast cancer MCF-7 cells and promote the apoptosis of MCF-7 cells by inhibiting the activation of the Akt signaling pathway. Therefore, EPS1-1 can be used as a potential new drug or adjuvant drug for the treatment of breast cancer.

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Effect of Eriodictyol on Retinoblastoma via the PI3K/Akt Pathway

Journal of Healthcare Engineering ◽

10.1155/2021/6091585 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Shu Wen ◽

Meng Hu ◽

Yan Xiong

Keyword(s):

Anticancer Activity ◽

Signaling Pathway ◽

Vision Loss ◽

Akt Signaling ◽

Migration And Invasion ◽

Dependent Manner ◽

Akt Signaling Pathway ◽

Anticancer Effects ◽

Induced Apoptosis ◽

Y79 Cells

Retinoblastoma (RB) is one of the most common intraocular malignancies in children, which causes vision loss and even threatens life. Eriodictyol is a natural flavonoid with strong anticancer activity. Some studies have shown that eriodictyol exerts anticancer effects in glioma, colon cancer, and lung cancer; however, no studies have reported the anticancer effects of eriodictyol on RB. Therefore, the aim of this study was to investigate the anticancer activity of eriodictyol against the RB Y79 cell line and its potential mechanism of action. Interestingly, we found that eriodictyol inhibited the proliferation, migration, and invasion of Y79 cells in a dose-dependent manner and decreased the expression of MMP-2 and MMP-9 proteins in the cells. In addition, eriodictyol-induced apoptosis in Y79 cells was assessed by flow cytometry and immunoblotting. Here, our study revealed that eriodictyol dose dependently inhibited the activation of the PI3K/Akt signaling pathway. Notably, the effect of eriodictyol on RB apoptosis was reversed by a PI3K agonist 740 Y-P. In conclusion, our study shows that eriodictyol effectively inhibits proliferation, migration, and invasion and induces apoptosis in RB cell lines, which may be the result of blocking the PI3K/Akt signaling pathway. Thus, eriodictyol may provide a new theoretical basis for exploring targeted antitumor natural therapies.

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Chidamide Inhibits Cell Proliferation via the PI3K/AKT Pathway in K562 Cells Based on Network Pharmacology and Experimental Validation

Current Pharmaceutical Design ◽

10.2174/1381612827666210701152250 ◽

2021 ◽

Vol 27 ◽

Author(s):

Simin Liang ◽

Xiaojia Zhou ◽

Duo Cai ◽

Fernando Rodrigues-Lima ◽

Li Wang

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

K562 Cells ◽

Akt Signaling ◽

Akt Pathway ◽

Network Pharmacology ◽

Dependent Manner ◽

Akt Signaling Pathway ◽

Antitumor Effects

Background: Chidamide, a novel benzamide-type histone deacetylase (HDAC) inhibitor, exerts antitumor effects on several types of cancer. However, the role of Chidamide in chronic myeloid leukemia (CML) remains elusive. Therefore, the present study aimed to investigate the effects of Chidamide on CML cell proliferation and explore its underlying mechanism. Methods: Cell proliferation was assessed by CCK-8 assay, cell cycle distribution and apoptosis were detected by flow cytometry and the expression of related proteins was evaluated by western blot analysis. The potential mechanisms were systematically explored by the network-based pharmacological methods, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Results: The results revealed that Chidamide inhibited the proliferation of K562 cells in a dose- and time-dependent manner. In addition, Chidamide blocked cells in the G0/G1 phase via downregulating cyclin‑dependent kinase 4, and induced apoptosis via upregulating Bax and downregulating of Bcl-2. Additionally, using network-based pharmacological methods, we found that PI3K/AKT signaling pathway is involved and significantly related to cell proliferation in CML. Intriguingly, cell treatment with Chidamide suppressed the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway via decreasing the levels of phosphorylated (p)-PI3K and p-AKT. Moreover, insulin-like growth factor 1 (IGF-1), a PI3K/AKT activator, reversed the inhibitory effects of Chidamide on K562 cell proliferation. Conclusion: The study demonstrated that Chidamide may inhibit the proliferation of K562 cells by promoting cell cycle arrest and apoptosis via suppressing the PI3K/AKT pathway, suggesting that Chidamide could be a promising approach to the treatment of CML.

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Licochalcone A inhibits the migration and invasion of human lung cancer cells via inactivation of the Akt signaling pathway with downregulation of MMP-1/-3 expression

Tumor Biology ◽

10.1007/s13277-014-2519-3 ◽

2014 ◽

Vol 35 (12) ◽

pp. 12139-12149 ◽

Cited By ~ 17

Author(s):

Hung-Che Huang ◽

Lo-Lin Tsai ◽

Jen-Pi Tsai ◽

Shu-Ching Hsieh ◽

Shun-Fa Yang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Human Lung ◽

Akt Signaling ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Migration And Invasion ◽

Akt Signaling Pathway ◽

Human Lung Cancer Cells

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Girdin regulates the migration and invasion of glioma cells via the PI3K-Akt signaling pathway

Molecular Medicine Reports ◽

10.3892/mmr.2015.4049 ◽

2015 ◽

Vol 12 (4) ◽

pp. 5086-5092 ◽

Cited By ~ 7

Author(s):

WEIMIN NI ◽

YAN FANG ◽

LEI TONG ◽

ZHAOXUE TONG ◽

FUXIN YI ◽

...

Keyword(s):

Signaling Pathway ◽

Glioma Cells ◽

Akt Signaling ◽

Migration And Invasion ◽

Akt Signaling Pathway

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PI3K/AKT Signaling Pathway Mediates the Proliferation, Migration and Invasion of Papillary Craniopharyngioma Cells

10.21203/rs.3.rs-119581/v1 ◽

2020 ◽

Author(s):

Lin Zhou ◽

Cheng Xing Yang ◽

Lin Chun Fang ◽

You Yuan Bao ◽

Zhi Gang Wang ◽

...

Keyword(s):

Signaling Pathway ◽

Akt Signaling ◽

Cell Counting ◽

Migration And Invasion ◽

Specific Cell ◽

Primary Cells ◽

Akt Signaling Pathway ◽

Phosphatidylinositol 3 Kinase ◽

Growth And Survival ◽

Pi3k Signaling Pathway

Abstract Objective:Craniopharyngiomas are rare, histologically benign but clinically challenging neoplasms. Here, we aimed to interrogate the effect and significance of Phosphatidylinositol-3-kinase (PI3K) signaling pathway on papillary craniopharyngioma (PCP) cell growth and survival.Methods: We used Western blotting (WB) experiments to evaluate the expression of the PI3K/protein kinase B (AKT) in Craniopharyngiomas tissues, relative to health tissues. Primary tumor cells were obtained from fresh PCP samples by cell culture and then determined by cell morphology, immunofluorescence staining and expression of specific cell markers. In this study, PCP cell lines, isolated from fresh PCP samples, were treated with different concentrations of LY294002, a PI3K/AKT signaling inhibitor, to evaluate their proliferation, migration and invasion. We determined the cell proliferation using Cell Counting Kit-8 and colony formation. We then used flow cytometry to evaluate cell apoptosis and cell cycle. In addition, cell migration and invasion levels were determined by wound healing and Transwell assays, respectively.Results: Our data demonstrated that the expression of phosphorylated-PI3K/AKT was upregulated in human craniopharyngioma tissues compared to the normal control tissues. Immunofluorescence assays showed the presence of cytokeratin (pan CK) and vimentin protein (VIM) in the PCP primary cells. Furthermore, inhibition of PI3K/AKT signaling blocks the proliferation, migration and invasion of the PCP primary cells.Conclusions:Taken together, our data robustly demonstrates that the PI3K/AKT signaling pathway mediates the proliferation, migration and invasion of the PCP cells.

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Macamide B Pretreatment Attenuates Neonatal Hypoxic-Ischemic Brain Damage of Mice Induced Apoptosis by Regulates Autophagy Via The PI3K/AKT Signaling Pathway

10.21203/rs.3.rs-952715/v1 ◽

2021 ◽

Author(s):

Xiaoxia Yang ◽

Mengxia Wang ◽

Qian Zhou ◽

Yanxian Bai ◽

Jing Liu ◽

...

Keyword(s):

Signaling Pathway ◽

Brain Damage ◽

Infarct Volume ◽

Neuroprotective Effect ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Ischemic Brain Damage ◽

Ischemic Brain ◽

Induced Apoptosis ◽

The Impact

Abstract Lepidium meyenii (Maca) is an annual or biennial herb from South America that is a member of the genus Lepidium L. in the family Cruciferae. This herb has antioxidant, anti-apoptotic, and enhances autophagy functions and can prevent cell death, and protect neurons from ischemic damage. Macamide B, an effective active ingredient of maca, has a neuroprotective role in neonatal hypoxic-ischemic brain damage (HIBD), and the underlying mechanism of its neuroprotective effect is not yet known. The purpose of this study is to explore the impact of macamide B on HIBD-induced autophagy and apoptosis and its potential mechanism for neuroprotection. The modified Rice-Vannucci method was used to induce HIBD on 7-day-old (P7) macamide B and vehicle-pretreated pups. TTC staining was used to evaluate the cerebral infarct volume of pups, brain water content was measured to evaluate the neurological function of pups, neurobehavioral testing was used to assess functional recovery after HIBD, TUNEL and FJC staining was used to detect cell autophagy and apoptosis, and western blot analysis was used to detect the expression levels of the pro-survival signaling pathway phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and autophagy and the apoptosis-related proteins. The results show that macamide B pretreatment can significantly decrease brain damage, improve the recovery of neural function after HIBD. At the same time, macamide B pretreatment can induce the activation of PI3K/AKT signaling pathway after HIBD, enhance autophagy, and reduce hypoxic-ischemic (HI)-induced apoptosis. In addition, 3-methyladenine (3-MA), an inhibitor of PI3K/AKT signaling pathway, significantly inhibits the increase in autophagy levels, aggravates HI-induced apoptosis, and reverses the neuroprotective effect of macamide B on HIBD. Our data indicate that macamide B pretreatment might regulate autophagy through PI3K/AKT signaling pathway, thereby reducing HIBD-induced apoptosis and exerting neuroprotective effects on neonatal HIBD. Macamide B may become a new drug for the prevention and treatment of HIBD.

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