Pro-apoptotic and pro-autophagic effects of the Aurora kinase A inhibitor alisertib (MLN8237) on human osteosarcoma U-2 OS and MG-63 cells through the activation of mitochondria-mediated pathway and inhibition of p38 MAPK/PI3K/Akt/mTOR signaling pathway

Osteosarcoma is the most common primary malignancy of bone in children and the elderly. Recently, more and more researches have demonstrated that Ginsenoside Rg3 (Rg3) is involved in chemotherapy resistance in many cancer, making it a promising Chinese herbal monomer for oncotherapy. In this study, we investigated the efficacy of Rg3 in human osteosarcoma cell lines (MG-63, U-2OS, and SaOS-2). Cell proliferation was measured by CCK8 assay. The migration of cells was examined using the scratch assay method. Quantification of apoptosis was assessed further by flow cytometry. In addition, the expression of apoptosis-related genes (caspase9, caspase3, Bcl2, and Bax) were investigated using RT-PCR. We further investigated the protein level expression of Bcl 2, cleaved-caspase3, and PI3K/AKT/mTOR signaling pathway factors by Western blot assay. Our results revealed that Rg3 inhibited the proliferation and migration of human osteosarcoma cells and induced apoptosis in a concentration- and time-dependent manner. Western blot results showed that Rg3 reduced the protein expression of Bcl2 and PI3K/AKT/mTORbut increased the levels of cleaved-caspase3. Therefore, we hypothesized Rg3 inhibits the proliferation of osteosarcoma cell line and induces their apoptosis by affecting apoptosis-related genes (Bcl2, caspase3) as well as the PI3K/AKT/mTOR signaling pathway. To conclude, Rg3 is a new therapeutic agent against osteosarcoma.

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Silencing of Aurora kinase A by RNA interference inhibits tumor growth in human osteosarcoma cells by inducing apoptosis and G2/M cell cycle arrest

Oncology Reports ◽

10.3892/or.2014.2986 ◽

2014 ◽

Vol 31 (3) ◽

pp. 1249-1254 ◽

Cited By ~ 13

Author(s):

ZHENHUAN JIANG ◽

JIANNONG JIANG ◽

HUILIN YANG ◽

ZHIJUN GE ◽

QIANG WANG ◽

...

Keyword(s):

Cell Cycle ◽

Rna Interference ◽

Aurora Kinase ◽

Osteosarcoma Cells ◽

M Cell ◽

Aurora Kinase A ◽

Human Osteosarcoma ◽

Cycle Arrest ◽

Human Osteosarcoma Cells ◽

Kinase A

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Aurora kinase A suppresses metabolic stress-induced autophagic cell death by activating mTOR signaling in breast cancer cells

Oncotarget ◽

10.18632/oncotarget.2241 ◽

2014 ◽

Vol 5 (17) ◽

pp. 7498-7511 ◽

Cited By ~ 18

Author(s):

Ling-Zhi Xu ◽

Zi-Jie Long ◽

Fei Peng ◽

Yang Liu ◽

Jie Xu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Metabolic Stress ◽

Aurora Kinase ◽

Mtor Signaling ◽

Autophagic Cell Death ◽

Aurora Kinase A ◽

Kinase A

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Fenvalerate triggers Parkinson-like symptom during zebrafish development through initiation of autophagy and p38 MAPK/mTOR signaling pathway

Chemosphere ◽

10.1016/j.chemosphere.2019.125336 ◽

2020 ◽

Vol 243 ◽

pp. 125336 ◽

Cited By ~ 1

Author(s):

Jiansheng Zhu ◽

Rong Xia ◽

Zhongwei Liu ◽

Jiemiao Shen ◽

Xing Gong ◽

...

Keyword(s):

Signaling Pathway ◽

P38 Mapk ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Zebrafish Development

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ISL1 promoted tumorigenesis and EMT via Aurora kinase A-induced activation of PI3K/AKT signaling pathway in neuroblastoma

Cell Death and Disease ◽

10.1038/s41419-021-03894-3 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Mengzhen Li ◽

Chengtao Sun ◽

Xiaoyun Bu ◽

Yi Que ◽

Lian Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Malignant Tumors ◽

Aurora Kinase ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Aurora Kinase A ◽

Kinase A

AbstractNeuroblastoma (NB) is the most common extracranial solid malignancy in children and its mortality rate is relatively high. However, driver genes of NB are not clearly identified. Using bioinformatics analysis, we determined the top 8 differentially expressed genes (DEGs) in NB, including GFAP, PAX6, FOXG1, GAD1, PTPRC, ISL1, GRM5, and GATA3. Insulin gene enhancer binding protein 1 (ISL1) is a LIM homeodomain transcription factor which has been found to be highly expressed in a variety of malignant tumors, but the function of ISL1 in NB has not been fully elucidated. We identified ISL1 as an oncogene in NB. ISL1 is preferentially upregulated in NB tissues compared with normal tissues. High ISL1 expression is significantly associated with poor outcome of NB patients. Knockdown of ISL1 markedly represses proliferation and induces cell apoptosis in vitro, and suppresses tumorigenicity in vivo, while overexpression of ISL1 has the opposite effects. Mechanistically, we demonstrate that ISL1 promotes cell proliferation and EMT transformation through PI3K/AKT signaling pathway by upregulating Aurora kinase A (AURKA), a serine-threonine kinase that is essential for the survival of NB cells. The blockade of AURKA attenuates the function of ISL1 overexpression in the regulation of cell proliferation and migration, Conclusively, this study showed that ISL1 targeted AURKA to facilitate the development of NB, which provided new insights into the tumorigenesis of NB. Thus, ISL1 may be a promising therapeutic target in the future.

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Dieckol exerts anticancer activity in human osteosarcoma (MG-63) cells through the inhibition of PI3K/AKT/mTOR signaling pathway

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2021.07.019 ◽

2021 ◽

Author(s):

Shouqiang Zhang ◽

Hui Ren ◽

Hanting Sun ◽

Songhua Cao

Keyword(s):

Anticancer Activity ◽

Signaling Pathway ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Human Osteosarcoma

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Effects of Aurora kinase A on mouse decidualization via Stat3-plk1-cdk1 pathway

Reproductive Biology and Endocrinology ◽

10.1186/s12958-021-00847-5 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Peng-Chao Wang ◽

Si-Ting Chen ◽

Zeng-Ming Yang

Keyword(s):

Signaling Pathway ◽

Aurora Kinase ◽

Aurora A ◽

Aurora Kinase A ◽

Protein Levels ◽

Decidual Cells ◽

Implantation Sites ◽

Kinase A

Abstract Background Decidualization is essential to the successful pregnancy in mice. The molecular mechanisms and effects of Aurora kinase A (Aurora A) remain poorly understood during pregnancy. This study is the first to investigate the expression and role of Aurora A during mouse decidualization. Methods Quantitative real time polymerase chain reaction, western blotting and in situ hybridization were used to determine the expression of Aurora A in mouse uteri. Aurora A activity was inhibited by Aurora A inhibitor to explore the role of Aurora A on decidualization via regulating the Aurora A/Stat3/Plk1/Cdk1 signaling pathway. Results Aurora A was strongly expressed at implantation sites compared with inter-implantation sites. Furthermore, Aurora A was also significantly increased in oil-induced deciduoma compared with control. Both Aurora A mRNA and protein were significantly increased under in vitro decidualization. Under in vitro decidualization, Prl8a2, a marker of mouse decidualization, was significantly decreased by TC-S 7010, an Aurora A inhibitor. Additionally, Prl8a2 was reduced by Stat3 inhibitor, Plk1 inhibitor and Cdk1 inhibitor, respectively. Moreover, the protein levels of p-Stat3, p-Plk1 and p-Cdk1 were suppressed by TC-S 7010. The protein levels of p-Stat3, p-Plk1 and p-Cdk1 were also suppressed by S3I-201, a Stat3 inhibitor). SBE 13 HCl (Plk1 inhibitor) could reduce the protein levels of p-Plk1 and p-Cdk1. Collectively, Aurora A could regulate Stat3/Plk1/Cdk1 signaling pathway. Conclusion Our study shows that Aurora A is expressed in decidual cells and should be important for mouse decidualization. Aurora A/Stat3/Plk1/Cdk1 signaling pathway may be involved in mouse decidualization.

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