Cytotoxicity of portoamides in human cancer cells and analysis of the molecular mechanisms of action

Lung cancer is the common malignant tumor with the highest death rate in the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a potential anticancer agent induces selective apoptotic death of human cancer cells. Unfortunately, approximately half of lung cancer cell lines are intrinsically resistant to TRAIL-induced cell death. In this study, we identified RuvBL1 as a repressor of c-Jun/AP-1 activity, contributing to TRAIL resistance in lung cancer cells. Knocking down RuvBL1 effectively sensitized resistant cells to TRAIL, and overexpression of RuvBL1 inhibited TRAIL-induced apoptosis. Moreover, there was a negative correlation expression between RuvBL1 and c-Jun in lung adenocarcinoma by Oncomine analyses. High expression of RuvBL1 inversely with low c-Jun in lung cancer was associated with a poor overall prognosis. Taken together, our studies broaden the molecular mechanisms of TRAIL resistance and suggest the application of silencing RuvBL1 synergized with TRAIL to be a novel therapeutic strategy in lung cancer treatment.

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EGFR signal transactivation in cancer cells

Biochemical Society Transactions ◽

10.1042/bst0311203 ◽

2003 ◽

Vol 31 (6) ◽

pp. 1203-1208 ◽

Cited By ~ 284

Author(s):

O.M. Fischer ◽

S. Hart ◽

A. Gschwind ◽

A. Ullrich

Keyword(s):

Growth Factor ◽

Cancer Cells ◽

Cross Talk ◽

Molecular Mechanisms ◽

Human Cancer ◽

Growth Factor Receptor ◽

Cell Types ◽

General Concept ◽

Human Carcinoma ◽

Human Cancer Cells

The EGFR (epidermal growth factor receptor) plays a key role in the regulation of essential normal cellular processes and in the pathophysiology of hyperproliferative diseases such as cancer. Recent investigations have demonstrated that GPCRs (G-protein-coupled receptors) are able to utilize the EGFR as a downstream signalling partner in the generation of mitogenic signals. This cross-talk mechanism combines the broad diversity of GPCRs with the signalling capacities of the EGFR and has emerged as a general concept in a multitude of cell types. The molecular mechanisms of EGFR signal transactivation involve processing of transmembrane growth factor precursors by metalloproteases which have been recently identified as members of the ADAM (adisintegrin and metalloprotease) family of zinc-dependent proteases. Subsequently, the EGFR transmits signals to prominent downstream pathways, such as mitogen-activated protein kinases, the phosphoinositide 3-kinase/Akt pathway and modulation of ion channels. Analysis of GPCR-induced EGFR activation in more than 60 human carcinoma cell lines derived from different tissues has demonstrated the broad relevance of this signalling mechanism in cancer. Moreover, EGFR signal transactivation was linked to diverse biological processes in human cancer cells, such as cell proliferation, migration and anti-apoptosis. Together with investigations revealing the importance of this GPCR–EGFR cross-talk mechanism in cardiac hypertrophy, Helicobacter pylori-induced pathophysiological processes and cystic fibrosis, these findings support an important role for GPCR ligand-dependent EGFR signal transactivation in diverse pathophysiological disorders.

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Synergetic antineoplastic action of doxorubicin and fullerene C60 as means of its delivery towards human cancer cells in vitro: cellular and molecular mechanisms

Studia Biologica ◽

10.30970/sbi.0701.240 ◽

2013 ◽

Vol 7 (1) ◽

pp. 5-20

Author(s):

R. R. Panchuk ◽

◽

V. V. Chumak ◽

N. R. Skorokhyd ◽

L. V. Lehka ◽

...

Keyword(s):

Cancer Cells ◽

Molecular Mechanisms ◽

Human Cancer ◽

Fullerene C60 ◽

Antineoplastic Action ◽

Human Cancer Cells

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Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells

Oncogene ◽

10.1038/onc.2010.183 ◽

2010 ◽

Vol 29 (31) ◽

pp. 4378-4387 ◽

Cited By ~ 80

Author(s):

R Puca ◽

L Nardinocchi ◽

D Givol ◽

G D'Orazi

Keyword(s):

Cancer Cells ◽

Molecular Mechanisms ◽

Human Cancer ◽

Human Cancer Cells

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Cinnamon bark extract suppresses metastatic dissemination of cancer cells through inhibition of glycolytic metabolism

10.1101/2021.03.25.437098 ◽

2021 ◽

Author(s):

Yuki Konno ◽

Ami Maruyama ◽

Masaru Tomita ◽

Hideki Makinoshima ◽

Joji Nakayama

Keyword(s):

Cancer Cells ◽

Molecular Mechanisms ◽

Human Cancer ◽

Bark Extract ◽

Glycolytic Metabolism ◽

Cinnamon Bark ◽

Metastatic Dissemination ◽

Invasion And Migration ◽

Human Cancer Cells ◽

And Migration

AbstractMetastasis, a leading contributor to the morbidity of cancer patients, occurs through multiple steps. As each of these steps is promoted by different molecular mechanisms, blocking metastasis needs to target each of these steps. Here we report that cinnamon bark extract (CBE) has a suppressor effect on metastatic dissemination of cancer cells. Though a zebrafish embryo screen which utilizes conserved mechanisms between metastasis and zebrafish gastrulation for identifying anti-metastasis drugs, CBE was identified to interfere with gastrulation progression of zebrafish. A zebrafish xenotransplantation model of metastasis validated that CBE suppressed metastatic dissemination of human cancer cells (MDA-MB-231). Interestingly, quantitative metabolome analyses revealed that CBE-treated MDA-MB-231 cells disrupted the production of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P), which are intermediate metabolites of glycolytic metabolism. CBE decreased the expression of hexokinase 2 (HK2), which catalyzes G6P production, and pharmacological inhibition of HK2 suppressed cell invasion and migration of MDA-MB-231 cells. Taken together, CBE suppressed metastatic dissemination of human cancer cells by inhibiting glycolytic metabolism.

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Investigating Molecular Determinants of Cancer Cell Resistance to Ionizing Radiation Through an Integrative Bioinformatics Approach

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.620248 ◽

2021 ◽

Vol 9 ◽

Author(s):

Halil Ibrahim Toy ◽

Gökhan Karakülah ◽

Panagiota I. Kontou ◽

Hani Alotaibi ◽

Alexandros G. Georgakilas ◽

...

Keyword(s):

Ionizing Radiation ◽

Cancer Cells ◽

Cancer Cell ◽

Clinical Setting ◽

Molecular Mechanisms ◽

Radiation Treatment ◽

Human Cancer ◽

Cell Resistance ◽

Altered Expression ◽

Human Cancer Cells

Eradication of cancer cells through exposure to high doses of ionizing radiation (IR) is a widely used therapeutic strategy in the clinical setting. However, in many cases, cancer cells can develop remarkable resistance to radiation. Radioresistance represents a prominent obstacle in the effective treatment of cancer. Therefore, elucidation of the molecular mechanisms and pathways related to radioresistance in cancer cells is of paramount importance. In the present study, an integrative bioinformatics approach was applied to three publicly available RNA sequencing and microarray transcriptome datasets of human cancer cells of different tissue origins treated with ionizing radiation. These data were investigated in order to identify genes with a significantly altered expression between radioresistant and corresponding radiosensitive cancer cells. Through rigorous statistical and biological analyses, 36 genes were identified as potential biomarkers of radioresistance. These genes, which are primarily implicated in DNA damage repair, oxidative stress, cell pro-survival, and apoptotic pathways, could serve as potential diagnostic/prognostic markers cancer cell resistance to radiation treatment, as well as for therapy outcome and cancer patient survival. In addition, our findings could be potentially utilized in the laboratory and clinical setting for enhancing cancer cell susceptibility to radiation therapy protocols.

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High Mobility Group Box 1 (HMGB1) Induces Toll-Like Receptor 4-Mediated Production of the Immunosuppressive Protein Galectin-9 in Human Cancer Cells

Frontiers in Immunology ◽

10.3389/fimmu.2021.675731 ◽

2021 ◽

Vol 12 ◽

Author(s):

Anette Teo Hansen Selnø ◽

Stephanie Schlichtner ◽

Inna M. Yasinska ◽

Svetlana S. Sakhnevych ◽

Walter Fiedler ◽

...

Keyword(s):

Cancer Cells ◽

Transforming Growth Factor Beta ◽

Molecular Mechanisms ◽

Transforming Growth Factor ◽

Human Cancer ◽

High Mobility ◽

High Mobility Group ◽

Toll Like Receptor ◽

Autocrine Loop ◽

Human Cancer Cells

High mobility group box 1 (HMGB1) is a non-histone protein which is predominantly localised in the cell nucleus. However, stressed, dying, injured or dead cells can release this protein into the extracellular matrix passively. In addition, HMGB1 release was observed in cancer and immune cells where this process can be triggered by various endogenous as well as exogenous stimuli. Importantly, released HMGB1 acts as a so-called “danger signal” and could impact on the ability of cancer cells to escape host immune surveillance. However, the molecular mechanisms underlying the functional role of HMGB1 in determining the capability of human cancer cells to evade immune attack remain unclear. Here we report that the involvement of HMGB1 in anti-cancer immune evasion is determined by Toll-like receptor (TLR) 4, which recognises HMGB1 as a ligand. We found that HGMB1 induces TLR4-mediated production of transforming growth factor beta type 1 (TGF-β), displaying autocrine/paracrine activities. TGF-β induces production of the immunosuppressive protein galectin-9 in cancer cells. In TLR4-positive cancer cells, HMGB1 triggers the formation of an autocrine loop which induces galectin-9 expression. In malignant cells lacking TLR4, the same effect could be triggered by HMGB1 indirectly through TLR4-expressing myeloid cells present in the tumour microenvironment (e. g. tumour-associated macrophages).

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