scholarly journals Paris polyphylla 26 triggers G2/M phase arrest and induces apoptosis in HepG2 cells via inhibition of the Akt signaling pathway

2019 ◽  
Vol 47 (4) ◽  
pp. 1685-1695
Author(s):  
Qiang Li ◽  
Zifan He ◽  
Jiming Liu ◽  
Jianlong Wu ◽  
Guixiang Tan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Phase Arrest ◽  
Paris Polyphylla ◽  
M Phase ◽  
Related Proteins

Objectives Paris polyphylla 26 (PP-26) is a monomer purified from Paris polyphylla, which has traditionally been used as an antimicrobial, hemostatic, and anticancer agent in China. The anti-proliferation effect and underlying molecular mechanism of PP-26 were investigated in vitro. Methods The effects of PP-26 on various tumor cells were detected by MTT assay. PP-26-affected cell cycle and cell cycle-related proteins in HepG2 cells were detected by flow cytometry and western blotting, respectively. Apoptosis in response to PP-26 was assessed by Hoechst 33258 staining and flow cytometry. PP-26-affected apoptosis-related proteins and Akt signaling were detected by western blotting. The inhibitory effect of PP-26 on HepG2 cells, when combined with 5-fluorouracil (5-FU), was also assessed. Results PP-26 inhibited proliferation of HepG2 cells in a dose-dependent manner by triggering G2/M-phase arrest. Moreover, PP-26 induced apoptosis of HepG2 cells. Expression levels of apoptosis proteins caspase 9, caspase 3, PARP, Bcl-2, Bcl-xL, and Mcl-1 were downregulated, while the expression level of apoptosis protein Bax was upregulated. Expression levels of p-Akt, p-GSK-3β, and p-Foxo3 were downregulated. Combination with PP-26 enhanced 5-FU inhibition of HepG2 cell proliferation. Conclusions PP-26 triggers G2/M-phase arrest and induces apoptosis in HepG2 cells via inhibition of the Akt signaling pathway.

scholarly journals Pinocembrin Inhibits the Proliferation and Metastasis of Breast Cancer via Suppression of the PI3K/AKT Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinbing Zhu ◽  
Rongnian Li ◽  
Chen Wang ◽  
Shuo Zhou ◽  
Yujia Fan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Anticancer Activities ◽  
Phase Arrest ◽  
Low Concentrations ◽  
M Phase

The survival rate of breast cancer (BC) patients remains poor, thus the identification of safe and effective new drugs is crucial to improve therapeutic outcomes and overall survival. Pinocembrin (PCB), a pharmacologically active ingredient of Pinus heartwood, Eucalyptus, Euphorbia, Populus, and Sparattosperma leucanthum, has been widely applied for the treatment of various diseases and possesses anticancer activities. In vitro assays were performed to investigate the antiproliferation and antimetastasis activities of PCB in BC cells. A tumorigenesis assay with the use of murine BC models was performed to assess the antiproliferation activities of PCB in vivo. Moreover, the molecular mechanisms underlying the anticancer activities of PCB in BC cells were explored. The results showed that the anti-inhibitory and antiproliferation activities of PCB in BC might involve cell cycle (G2/M phase) arrest and apoptosis. PCB downregulated the expression levels of proteins involved in cell cycle progression and apoptosis, including cyclinB1, Cdc2, PARP1, Bcl-2, and survivin, and upregulated protein levels of cleaved PARP1, cleaved caspase3, cleaved caspase9, and BAX. In a murine subcutaneous tumor model, PCB suppressed the growth of MCF-7 cells in vivo. Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. Mechanistically, PCB administration was correlated to suppression of the PI3K/AKT signaling pathway. Inhibition of the proliferation of BC cells by PCB involved cell cycle (G2/M phase) arrest and apoptosis in vitro and in vivo. Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. These findings suggest that PCB might be an effective agent for treatment of BC patients.

scholarly journals The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Linwen Zhu ◽  
Zhe Li ◽  
Xiuchong Yu ◽  
Yao Ruan ◽  
Yijing Shen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gastric Cancer Cells ◽  
Qrt Pcr

Abstract Background Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice. Results tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth. Conclusions tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.

scholarly journals Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K/AKT signaling pathway

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Dongyong Yang ◽  
Yanqing Wang ◽  
Yajing Zheng ◽  
Fangfang Dai ◽  
Shiyi Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Structural Damage ◽  
Polycystic Ovary ◽  
Serum Insulin ◽  
Tumor Cell Line ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Abstract Background Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-aged women worldwide, however, the mechanisms and progression of PCOS still unclear due to its heterogeneous nature. Using the human granulosa-like tumor cell line (KGN) and PCOS mice model, we explored the function of lncRNA UCA1 in the pathological progression of PCOS. Results CCK8 assay and Flow cytometry were used to do the cell cycle, apoptosis and proliferation analysis, the results showed that UCA1 knockdown in KGN cells inhibited cell proliferation by blocking cell cycle progression and promoted cell apoptosis. In the in vivo experiment, the ovary of PCOS mice was injected with lentivirus carrying sh-UCA1, the results showed that knockdown of lncRNA UCA1 attenuated the ovary structural damage, increased the number of granular cells, inhibited serum insulin and testosterone release, and reduced the pro-inflammatory cytokine production. Western blot also revealed that UCA1 knockdown in PCOS mice repressed AKT activation, inhibitor experiment demonstrated that suppression of AKT signaling pathway, inhibited the cell proliferation and promoted apoptosis. Conclusions Our study revealed that, in vitro, UCA1 knockdown influenced the apoptosis and proliferation of KGN cells, in vivo, silencing of UCA1 regulated the ovary structural damage, serum insulin release, pro-inflammatory production, and AKT signaling pathway activation, suggesting lncRNA UCA1 plays an important role in the pathological progression of PCOS.

scholarly journals MicroRNA-561 Affects Proliferation and Cell Cycle Transition Through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC

2020 ◽  
Vol 28 (2) ◽  
pp. 147-159 ◽  
Author(s):  
ZiJun Liao ◽  
Qi Zheng ◽  
Ting Wei ◽  
YanBing Zhang ◽  
JieQun Ma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Exogenous Expression ◽  
Induced Apoptosis

MicroRNAs (miRNAs) play crucial roles in tumorigenesis and tumor progression. miR-561 has been reported to be downregulated in gastric cancer and affects cancer cell proliferation and metastasis. However, the role and underlying molecular mechanism of miR-561 in human non-small cell lung cancer (NSCLC) remain unknown and need to be further elucidated. In this study, we discovered that miR-561 expression was downregulated in human NSCLC tissues and cell lines. The overexpression of miR-561 inhibited NSCLC cell proliferation and cell cycle G1/S transition and induced apoptosis. The inhibition of miR-561 facilitated cell proliferation and G1/S transition and suppressed apoptosis. miR-561 expression was inversely correlated with P-REX2a expression in NSCLC tissues. P-REX2a was confirmed to be a direct target of miR-561 using a luciferase reporter assay. The overexpression of miR-561 decreased P-REX2a expression, and the suppression of miR-561 increased P-REX2a expression. Particularly, P-REX2a silencing recapitulated the cellular and molecular effects observed upon miR-561 overexpression, and P-REX2a overexpression counteracted the effects of miR-561 overexpression on NSCLC cells. Moreover, both exogenous expression of miR-561 and silencing of P-REX2a resulted in suppression of the PTEN/AKT signaling pathway. Our study demonstrates that miR-561 inhibits NSCLC cell proliferation and G1/S transition and induces apoptosis through suppression of the PTEN/AKT signaling pathway by targeting P-REX2a. These findings indicate that miR-561 plays a significant role in NSCLC progression and serves as a potential therapeutic target for NSCLC.

Natural borneol enhances bisdemethoxycurcumin-induced cell cycle arrest in the G2/M phase through up-regulation of intracellular ROS in HepG2 cells

2015 ◽  
Vol 6 (3) ◽  
pp. 740-748 ◽  
Author(s):  
Jianping Chen ◽  
Lin Li ◽  
Jianyu Su ◽  
Tianfeng Chen
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Hepg2 Cells ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
Intracellular Ros ◽  
M Phase

Natural borneol and bisdemethoxycurcumin in combination induces G2/M phase arrest in HepG2 cells.

scholarly journals Cinobufacini Injection Suppresses the Proliferation of Human Osteosarcoma Cells by Inhibiting PI3K/Akt Signaling Pathway

2021 ◽  
Author(s):  
Changbao Chen ◽  
Yu Zhai ◽  
Yuru Chen ◽  
Ye Yuan ◽  
Shengyu Hua ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Western Blot ◽  
Signaling Pathway ◽  
Blot Analysis ◽  
Akt Signaling ◽  
Rna Seq ◽  
Akt Signaling Pathway ◽  
Cycle Arrest ◽  
Mg63 Cells ◽  
Cinobufacini Injection

Abstract Background: Cinobufacini injection (CI), an aqueous extraction from the Cutis Bufonis, is broadly used in clinical treatment of cancer in China. However, the underlying molecular mechanisms of CI in treating osteosarcoma (OS) remain unclear. Aberrant activation of PI3K-AKT signaling pathway is the cause of many types of cancer, including OS. Therefore, we investigated the effect of CI on proliferation, apoptosis and cell cycle of OS cells and elucidated the molecular mechanism of CI in inhibiting OS cells. Methods: Cell proliferation of U2OS and MG63 cells after CI treatment was measured by CCK-8 assay, colony formation and morphological changes. Additionally, the cell cycle arrest and apoptosis induced by CI, were determined by FACS and Western blot analysis. The mechanisms of CI on OS were evaluated by RNA-seq and Western blot analysis. Results: We founf that CI reduced the proliferation of U2OS and MG63 cells in a dose- and time- dependent manner. Furthermore, CI induced the U2OS cells cycle arrest in G0/G1 phase, but the MG63 cells cycle arrest in G2/M phase. Consequently, CI triggered the apoptosis in both OS cells, with enhanced caspase-3 activity and decreased expression of Bcl-2/Bax. In addition, RNA-seq data indicated that PI3K-Akt signaling pathway played an essential role in CI treatment. Moreover PI3K and phosphorylation of AKT (p-AKT) were significantly down-regulated by CI in both OS cells. Conclusions: These results indicate that CI significantly inhibited the proliferation, induced the cell cycle arrest, as well as apoptosis in human OS cells, which is mediated by the inactivation of PI3K-Akt signaling pathway. These findings suggest that CI may have potential for the treatment of OS.

scholarly journals α-Mangostin Induces Apoptosis and Inhibits Metastasis of Breast Cancer Cells via Regulating RXRα-AKT Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiuzhi Zhu ◽  
Jialin Li ◽  
Huiting Ning ◽  
Zhidong Yuan ◽  
Yue Zhong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Mangostin, which has the function of anti-inflammatory, antioxidant, and anticancer, etc, is one of the main active ingredients of the hull of the mangosteen. The main objective of the study was to elucidate its anti-cancer function and possible mechanism. α-Mangostin was separated and structurally confirmed. MTT method was used to check the effect of mangostin on breast cancer cell proliferation. Then the effect of α-Mangostin on the transcriptional activity of RXRα was tested by dual-luciferase reporter gene assay. And Western blot (WB) was used to detect the expression of apoptosis-related proteins or cell cycle-associated proteins after treatment. Also, this study was to observe the effects of α-Mangostin on the invasion of breast cancer cell line MDA-MB-231. α-Mangostin regulates the downstream effectors of the PI3K/AKT signaling pathway by degrading RXRα/tRXRα. α-Mangostin can trigger PARP cleavage and induce apoptosis, which may be related to the induction of upregulated BAX expression and downregulation of BAD and cleaved caspase-3 expression in MDA-MB-231 cells through blockade of AKT signaling. The experiments verify that α-Mangostin have evident inhibition effects of invasion and metastasis of MDA-MB-231 cells. Cyclin D1 was involved in the anticancer effects of α-Mangostin on the cell cycle in MDA-MB-231 cells. α-Mangostin induces apoptosis, suppresses the migration and invasion of breast cancer cells through the PI3K/AKT signaling pathway by targeting RXRα, and cyclin D1 has involved in this process.

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