Linking hyperosmotic stress and apoptotic sensitivity

Stöhr, Daniela; Rehm, Markus

doi:10.1111/febs.15520

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…Interestingly, DPSC lysate was able to effectively reduce the viability of lung cancer cells and induce apoptosis in a concentration-dependent manner. Western blot results showed that the expression levels of pro-apoptotic proteins in the 1:1 group of DPSC lysate were much higher than those in the other two lysate groups, probably because the high concentration of 1:1 DPSC lysate caused changes in the osmolarity of the cancer cell environment, leading to apoptosis [ 40 ]. Apoptosis is a programmed death and is an important self-stabilizing mechanism in organisms.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models

He,

Li,

She

et al. 2023

J Nanobiotechnol

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Background Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. Methods The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. Results DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. Conclusions DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models

He,

Li,

She

et al. 2023

J Nanobiotechnol

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“…We chose the liver cancer cell line HepG2 as the model cell type given that the cell line recapitulates characteristics of hepatoblasts as well as epithelial-like HCC 41 . Several previous studies showed that acute osmotic stress induces cell death 42,43 . Here we found HepG2 cells at all different compression levels after long-term treatment (5 days) not only survived better than under control conditions but also underwent a drastic morphological change (Fig.…”

Section: Hyperosmolarity-induced Volumetric Compression Drives Morpho...mentioning

confidence: 99%

Adaptation to volumetric compression drives hepatoblastoma cells to an apoptosis-resistant and invasive phenotype

Gong,

Ogino,

Leite

et al. 2023

Preprint

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Liver cancer involves tumor cells rapidly growing within a packed tissue environment. Patient tumor tissues reveal densely packed and deformed cells, especially at tumor boundaries, indicative of physical crowding and compression. It is not well understood how these physical signals modulate tumor evolution and therapeutic susceptibility. Here we investigate the impact of volumetric compression on liver cancer (HepG2) behavior. We find that conditioning cells under a highly compressed state leads to major transcriptional reprogramming, notably the loss of hepatic markers, the epithelial-to-mesenchymal transition (EMT)-like changes, and altered calcium signaling-related gene expression, over the course of several days. Biophysically, compressed cells exhibit increased Rac1-mediated cell spreading and cell-extracellular matrix interactions, cytoskeletal reorganization, increased YAP and β-catenin nuclear translocation, and dysfunction in cytoplasmic and mitochondrial calcium signaling. Furthermore, compressed cells are resistant to chemotherapeutics and desensitized to apoptosis signaling. Apoptosis sensitivity can be rescued by stimulated calcium signaling. Our study demonstrates that volumetric compression is a key microenvironmental factor that drives tumor evolution in multiple pathological directions and highlights potential countermeasures to re-sensitize therapy-resistant cells.Significance statementCompression can arise as cancer cells grow and navigate within the dense solid tumor microenvironment. It is unclear how compression mediates critical programs that drive tumor progression and therapeutic complications. Here, we take an integrative approach in investigating the impact of compression on liver cancer. We identify and characterize compressed subdomains within patient tumor tissues. Furthermore, using in vitro systems, we induce volumetric compression (primarily via osmotic pressure but also via mechanical force) on liver cancer cells and demonstrate significant molecular and biophysical changes in cell states, including in function, cytoskeletal signaling, proliferation, invasion, and chemoresistance. Importantly, our results show that compressed cells have impaired calcium signaling and acquire resistance to apoptosis, which can be countered via calcium mobilization.

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Inhibitory potential of nanoscale dental pulp stem cell lysate in lung cancer with risk of lymph node metastasis

He,

Li,

She

et al. 2023

Preprint

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Background Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on the proliferation, apoptosis, migration, and invasion of A549 lung cancer cells and its inhibitory effect on tumors in vivo. Methods The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. Results DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. Conclusions DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in A549 cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.

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Linking hyperosmotic stress and apoptotic sensitivity

Cited by 3 publications

References 16 publications

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models

Inhibitory effects of the nanoscale lysate derived from xenogenic dental pulp stem cells in lung cancer models

Adaptation to volumetric compression drives hepatoblastoma cells to an apoptosis-resistant and invasive phenotype

Inhibitory potential of nanoscale dental pulp stem cell lysate in lung cancer with risk of lymph node metastasis

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