Luteoloside induces G0/G1 arrest and pro-death autophagy through the ROS-mediated AKT/mTOR/p70S6K signalling pathway in human non-small cell lung cancer cell lines

Zhou, Menglu; Shen, Shuying; Zhao, Xin; Gong, Xingguo

doi:10.1016/j.bbrc.2017.10.042

Cited by 56 publications

(40 citation statements)

References 16 publications

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“…However, full-length BCAP31 inhibits caspase activity 38 , and in cancer, apoptosis-resistance mechanisms are used to evade cell death 39 . Aside from this, the Akt/mTOR/p70s6K pathway also play a significant role in cell autophagy 40 . However, there have been no predictive markers identified as yet that correlate with the clinical activity of novel targeted Akt or dual PI3K/mTOR agents, despite efforts to evaluate tumor molecular status in the early phases of therapeutic clinical trials 41 .…”

Section: Discussionmentioning

confidence: 99%

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

Wang

Jiang

et al. 2020

Sci Rep

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Non-small-cell lung cancer (NSCLC) represents most of lung cancers, is often diagnosed at an advanced metastatic stage. Therefore, exploring the mechanisms underlying metastasis is key to understanding the development of NSCLC. The expression of B cell receptor-associated protein 31 (BCAP31), calreticulin, glucose-regulated protein 78, and glucose-regulated protein 94 were analyzed using immunohistochemical staining of 360 NSCLC patients. It resulted that the high-level expression of the four proteins, but particularly BCAP31, predicted inferior overall survival. What's more, BCAP31 was closely associated with histological grade and p53 status, which was verified by seven cohorts of NSCLC transcript microarray datasets. Then, three NSCLC cell lines were transfected to observe behavior changes BCAP31 caused, we found the fluctuation of BCAP31 significantly influenced the migration, invasion of NSCLC cells. To identify the pathway utilized by BCAP31, Gene Set Enrichment Analysis was firstly performed, showing Akt/m-TOR/p70S6K pathway was the significant one, which was verified by immunofluorescence, kinase phosphorylation and cellular behavioral observations. Finally, the data of label-free mass spectroscopy implied that BCAP31 plays a role in a fundamental biological process. This study provides the first demonstration of BCAP31 as a novel prognostic factor related to metastasis and suggests a new therapeutic strategy for NSCLC.Lung cancer is one of the most prevalent neoplasms and the leading cause of cancer-related death worldwide, being responsible for nearly one in five cases 1 . Non-small-cell lung cancer (NSCLC) contributes to 85% of lung cancer cases. Owing to the absence of clinical symptoms and effective screening programs, most lung cancers are diagnosed at an advanced stage with metastasis. Targeted immunotherapy, including anti-angiogenic and checkpoint monoclonal antibodies or tyrosine kinase inhibitors, demonstrates better efficacy than traditional surgical treatment and radio-chemotherapy, although drug resistance and tumor heterogeneity remain significant problems, and metastasis remains the major cause of mortality 2 .It is therefore important to identify efficient symbolic markers of metastasis and therapeutic targets for NSCLC. Given the aberrant expression of specific genes in a variety of cancer types, restricted in testis or selected in normal tissue, cancer-testis antigens (CTAs) have emerged as efficient specific tumor targets which spare normal tissue from incurring damage during treatment 3 . Originally described in patients with malignant melanoma 4 , CTAs have been identified as biomarkers for a diverse range of cancers, including NSCLC 5 . Their expression is often coordinated 6 , and associated with poor clinical outcome 7 and advanced stage 8 , particularly metastasis 9 .with histological grade (p = 0.0009) and p53 status (p = 0.0058; Supplementary Table S1). However, there was no correlation between BCAP31 mRNA expression and NSCLC prognosis, which was inconsistent with our protein ...

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Section: Discussionmentioning

confidence: 99%

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

Wang

Jiang

et al. 2020

Sci Rep

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“…The expression of specific proteins was detected using western blot analysis. After cytisine treatment at the IC 50 concentration for different times (3,6,12, and 24 h), we collected the cells and added lysis buffer to lyse on ice for 30 min. Protein extracts were separated on 8-12% SDS-PAGE and then electro-transferred to nitrocellulose membranes (Sigma, St. Louis, MO, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…It is estimated that 1.8 million people died from this disease in 2018, accounting for 18.4% of total estimated cancer deaths [2]. Recently, the morbidity and mortality of lung carcinoma have noticeably increased [3]. Because lung cancer is typically advanced at the time of diagnosis, the feasibility of surgical resection is greatly limited, and systemic drug therapy is focussed on controlling symptoms and prolonging survival [4].…”

Section: Introductionmentioning

confidence: 99%

Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…In addition, Li et al suggested that activation of AKT/FOXM1/STMN1 pathway contributed to the resistance to tyrosine kinase inhibitors in lung cancer . Zhou et al proved that luteoloside induced G0/G1 phase arrest and cell death‐prone autophagy through ROS‐mediated AKT/mTOR/p70S6K signaling pathway in human NSCLC cell lines . And Zhou et al demonstrated that in the A549 cell line, apigenin inhibited cell proliferation, invasion and migration by targeting Akt .…”

Section: Discussionmentioning

confidence: 99%

Serous IFNA3 predicts unfavorable prognosis in lung cancer via abnormal activation of AKT signaling

Cong

2019

IUBMB Life

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This study addresses the demand through datamining The Cancer Genome Atlas (TCGA) database and elucidates mechanistic involvements of interferon alpha 8 (IFNA8) in lung cancer. The overall survival and disease-free survival of lung cancer patients in respect to IFNA8 expression level were analyzed. IFNA8 expression levels in both serum and tumor tissue were determined by real-time polymerase chain reaction. The diagnostic value of serous IFNA8 in lung cancer was assessed by receiver operating characteristic (ROC) curve analysis. Cell viability and proliferation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Cell Counting Kit-8 assays. in vivo pro-tumor effect of IFNA8 was evaluated using xenograft tumor model. The metastasis-prone behaviors were determined by Transwell chamber assay and tail vein-injection in mice. Protein levels of p-AKT, total AKT, and endogenous reference actin were analyzed by western blot. We uncovered high IFNA8 associated with unfavorable overall survival and disease-free survival in lung cancer patients from TCGA. We further characterized the aberrant over-expression of IFNA8 in both peripheral blood and solid tumor from our clinical patient panel, and ROC analysis suggested its potential diagnostic value. Ectopic over-expression of IFNA8 promoted viability and proliferation in both A549 and H1299 cells in vitro and accelerated xenograft tumor growth in vivo. Furthermore, IFNA8 facilitated migration, invasion, and metastasis of A549 cells in vivo. Mechanistically, we disclosed the over-activation of AKT signaling in IFNA8-proficient A549 cells, inhibition of which completely abolished the pro-tumor effects of IFNA8. We have identified IFNA8 as a novel biomarker for either diagnostic or prognostic purpose in lung cancer, which is mechanistically associated with abnormal activation of AKT signaling. K E Y W O R D SAKT signaling, biomarker, IFNA8, lung cancer

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Luteoloside induces G0/G1 arrest and pro-death autophagy through the ROS-mediated AKT/mTOR/p70S6K signalling pathway in human non-small cell lung cancer cell lines

Cited by 56 publications

References 16 publications

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

BCAP31, a cancer/testis antigen-like protein, can act as a probe for non-small-cell lung cancer metastasis

Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways

Serous IFNA3 predicts unfavorable prognosis in lung cancer via abnormal activation of AKT signaling

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