scholarly journals The solvent and treatment regimen of sodium selenite cause its effects to vary on the radiation response of human bronchial cells from tumour and normal tissues

2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Katrin Manda ◽  
Stephan Kriesen ◽  
Guido Hildebrandt
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Metabolic Activity ◽  
Sodium Selenite ◽  
Combined Treatment ◽  
Radiation Response ◽  
Cell Cycle Distribution ◽  
Normal Cells ◽  
Bronchial Cells

AbstractSodium selenite is often given to moderate the side effects of cancer therapy to enhance the cellular defence of non-cancerous cells. To determine whether sodium selenite during radiotherapy protects not only normal cells but also cancer cells, which would imply a reduction of the desired effect of irradiation on tumour during radiotherapy, the effect of the combined treatment of irradiation and sodium selenite was investigated. Human bronchial cells from carcinoma (A549) and normal tissue (BEAS-2B) were treated with sodium selenite and effects on growth and in combination with radiation on metabolic activity and cell cycle distribution were studied. The influence on radiosensitivity was determined via colony forming assays using different solvents of sodium selenite and treatment schedules. It was shown that sodium selenite inhibits growth and influences cell cycle distribution of both normal and tumour cells. Metabolic activity of normal cells decreased more rapidly compared to that of cancer cells. The influence of sodium selenite on radiation response depended on the different treatment schedules and was strongly affected by the solvent of the agent. It could be shown that the effect of sodium selenite on radiation response is strongly dependent on the respective experimental in vitro conditions and ranges from lead to an initially suspected but ultimately no real radioprotection to radiosensitizing up to no effect in one and the same cell line. This might be a reason for controversially described cell responses to radiation under the influence of sodium selenite in studies so far.

scholarly journals Chidamide Combined With Doxorubicin Induced p53-Driven Cell Cycle Arrest and Cell Apoptosis Reverse Multidrug Resistance of Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lixia Cao ◽  
Shaorong Zhao ◽  
Qianxi Yang ◽  
Zhendong Shi ◽  
Jingjing Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Combined Treatment ◽  
Tunel Staining ◽  
Cell Cycle Distribution ◽  
Cycle Arrest

The multidrug-resistant (MDR) phenotype is usually accompanied by an abnormal expression of histone deacetylase (HDAC). Given that HDAC is vital in chromatin remodeling and epigenetics, inhibiting the role of HDAC has become an important approach for tumor treatment. However, the effect of HDAC inhibitors on MDR breast cancer has not been elucidated. This study aim to demonstrate the potential of chidamide (CHI) combined with the chemotherapy drug doxorubicin (DOX) to overcome chemotherapeutic resistance of breast cancer in vitro and in vivo, laying the experimental foundation for the next clinical application. The results showed that, CHI combined with DOX showed significant cytotoxicity to MDR breast cancer cells in vitro and in vivo compared with the CHI monotherapy. The cell cycle distribution results showed that CHI caused G0/G1 cell cycle arrest and inhibited cell growth regardless of the addition of DOX. At the same time, annexin V staining and TUNEL staining results showed that CHI enhanced the number of cell apoptosis in drug-resistant cells. The western blot analysis found that p53 was activated in the CHI-treated group and combined treatment group, and then the activated p53 up-regulated p21, apoptosis regulator recombinant protein (Puma), and pro-apoptotic protein Bax, down-regulated the apoptotic proteins Bcl-xL and Bcl-2, and activated the caspase cascade to induce apoptosis.

scholarly journals Low-Frequency Magnetic Fields (LF-MFs) Inhibit Proliferation by Triggering Apoptosis and Altering Cell Cycle Distribution in Breast Cancer Cells

2020 ◽  
Vol 21 (8) ◽  
pp. 2952
Author(s):  
Aoshu Xu ◽  
Qian Wang ◽  
Tingting Lin
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Magnetic Fields ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Glycogen Synthase ◽  
Low Frequency ◽  
Cell Cycle Distribution ◽  
Cell Proliferation Inhibition

Breast cancer is a common malignancy threatening women’s health around the world. Despite improved treatments for different subtypes of breast tumors that have been put forward, there still exists a poor therapeutic response and prognosis. Magnetic fields, as a non-invasive therapy, have shown anti-tumor effects in vitro and in vivo; however, the detailed mechanisms involved are still not clear. In this study, we found that in exposure to low-frequency magnetic fields (LF-MFs) with an intensity of 1 mT and frequencies of 50, 125, 200, and 275 Hz, separately, the proliferation of breast cancer cells was inhibited and LF-MF with 200 Hz reached the optimum inhibition effect, on exposure time-dependently. Notably, we found that exposure to LF-MF led to MCF-7 and ZR-75-1 cell apoptosis and cell cycle arrest. Moreover, we also discovered that LF-MF effectively increased the level of reactive oxygen species (ROS), suppressed the PI3K/AKT signaling pathway, and activated glycogen synthase kinase-3β (GSK-3β). We demonstrated that the GSK3β activity contributed to LF-MF-induced cell proliferation inhibition and apoptosis, while the underlying mechanism was associated with the inhibition of PI3K/AKT through increasing the intracellular ROS accumulation. These results indicate that LF-MF with a specific frequency may be an attractive therapy to treat breast cancers.

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

2020 ◽  
Vol 20 ◽  
Author(s):  
En Xu ◽  
Hao Zhu ◽  
Feng Wang ◽  
Ji Miao ◽  
Shangce Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Dual Inhibitor ◽  
Induced Apoptosis

: Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

scholarly journals Cytotoxicity, Oxidative Stress, Cell Cycle Arrest, and Mitochondrial Apoptosis after Combined Treatment of Hepatocarcinoma Cells with Maleic Anhydride Derivatives and Quercetin

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Gabriela Carrasco-Torres ◽  
Rafael Baltiérrez-Hoyos ◽  
Erik Andrade-Jorge ◽  
Saúl Villa-Treviño ◽  
José Guadalupe Trujillo-Ferrara ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Maleic Anhydride ◽  
Cancer Cells ◽  
Combination Treatment ◽  
Malignant Tumors ◽  
Combined Treatment ◽  
Current Data ◽  
Carcinoma Cells ◽  
Hepatocellular Carcinoma Cells

The inflammatory condition of malignant tumors continually exposes cancer cells to reactive oxygen species, an oxidizing condition that leads to the activation of the antioxidant defense system. A similar activation occurs with glutathione production. This oxidant condition enables tumor cells to maintain the energy required for growth, proliferation, and evasion of cell death. The objective of the present study was to determine the effect on hepatocellular carcinoma cells of a combination treatment with maleic anhydride derivatives (prooxidants) and quercetin (an antioxidant). The results show that the combination of a prooxidant/antioxidant had a cytotoxic effect on HuH7 and HepG2 liver cancer cells, but not on either of two normal human epithelial cell lines or on primary hepatocytes. The combination treatment triggered apoptosis in hepatocellular carcinoma cells by activating the intrinsic pathway and causing S phase arrest during cell cycle progression. There is also clear evidence of a modification in cytoskeletal actin and nucleus morphology at 24 and 48 h posttreatment. Thus, the current data suggest that the combination of two anticarcinogenic drugs, a prooxidant followed by an antioxidant, can be further explored for antitumor potential as a new treatment strategy.

scholarly journals Antiproliferative Activity and Potential Mechanism of Marine-Sourced Streptoglutarimide H against Lung Cancer Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 79
Author(s):  
Hengju Ge ◽  
Di Zhang ◽  
Muran Shi ◽  
Xiaoyuan Lian ◽  
Zhizhen Zhang
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Antiproliferative Activity ◽  
Lung Cancer Cells ◽  
Potential Mechanism ◽  
Nucleotide Synthesis ◽  
Factor C ◽  
Antiglioma Activity

In 2019, streptoglutarimide H (SGH) was characterized as a new glutarimide from the secondary metabolites produced by a marine-derived actinomycete Streptomyces sp. ZZ741 and shown to have in vitro antiglioma activity. However, the antiproliferative activity and potential mechanism of SGH against lung cancer cells have not yet been characterized. This study demonstrated that SGH significantly inhibited the proliferation of different lung cancer cells. In terms of mechanism of action, SGH downregulated cell cycle- and nucleotide synthesis-related proteins to block cell cycle at G0/G1 phase, reduced the expression levels of glycolytic metabolic enzymes to inhibit glycolysis, and downregulated the important cancer transcription factor c-Myc and the therapeutic target deubiquitinase USP28. Potent anticancer activity and multiple mechanisms indicated SGH to be a novel antitumor compound against lung cancer cells.

scholarly journals Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage

2021 ◽  
Author(s):  
Xinrui Zhang ◽  
Mariana Bobeica ◽  
Michael Unger ◽  
Anastasia Bednarz ◽  
Bjoern Gerold ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Metabolic Activity ◽  
Focused Ultrasound ◽  
Double Strand Breaks ◽  
High Intensity Focused Ultrasound ◽  
Dna Double Strand Breaks ◽  
Strand Breaks

Abstract Purpose High-intensity focused ultrasound (HIFU/FUS) has expanded as a noninvasive quantifiable option for hyperthermia (HT). HT in a temperature range of 40–47 °C (thermal dose CEM43 ≥ 25) could work as a sensitizer to radiation therapy (RT). Here, we attempted to understand the tumor radiosensitization effect at the cellular level after a combination treatment of FUS+RT. Methods An in vitro FUS system was developed to induce HT at frequencies of 1.147 and 1.467 MHz. Human head and neck cancer (FaDU), glioblastoma (T98G), and prostate cancer (PC-3) cells were exposed to FUS in ultrasound-penetrable 96-well plates followed by single-dose X‑ray irradiation (10 Gy). Radiosensitizing effects of FUS were investigated by cell metabolic activity (WST‑1 assay), apoptosis (annexin V assay, sub-G1 assay), cell cycle phases (propidium iodide staining), and DNA double-strand breaks (γH2A.X assay). Results The FUS intensities of 213 (1.147 MHz) and 225 W/cm2 (1.467 MHz) induced HT for 30 min at mean temperatures of 45.20 ± 2.29 °C (CEM43 = 436 ± 88) and 45.59 ± 1.65 °C (CEM43 = 447 ± 79), respectively. FUS improves the effect of RT significantly by reducing metabolic activity in T98G cells 48 h (RT: 96.47 ± 8.29%; FUS+RT: 79.38 ± 14.93%; p = 0.012) and in PC-3 cells 72 h (54.20 ± 10.85%; 41.01 ± 11.17%; p = 0.016) after therapy, but not in FaDu cells. Mechanistically, FUS+RT leads to increased apoptosis and enhancement of DNA double-strand breaks compared to RT alone in T98G and PC-3 cells. Conclusion Our in vitro findings demonstrate that FUS has good potential to sensitize glioblastoma and prostate cancer cells to RT by mainly enhancing DNA damage.

The Potential Oncogenic and MLN4924-Resistant Effects of CSN5 on Cervical Cancer Cells

2021 ◽  
Author(s):  
Huilin Zhang ◽  
Ping He ◽  
Qing Zhou ◽  
Yan Lu ◽  
Bingjian Lu
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cervical Cancers ◽  
Cervical Cancer Cells

Abstract BackgroundsCSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet.MethodsData from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR-CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. CCK8, clone formation assay and cell cycle assay were also employed. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. Moreover, MLN4924 was applied in Siha and Hela with CSN5 overexpression.ResultsWe found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells.ConclusionsOur findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.

A novel PLK1 inhibitor onvansertib effectively sensitizes MYC-driven medulloblastoma to radiotherapy

2021 ◽  
Author(s):  
Dong Wang ◽  
Bethany Veo ◽  
Angela Pierce ◽  
Susan Fosmire ◽  
Krishna Madhavan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Tumor Growth ◽  
Radiation Treatment ◽  
Tumor Regression ◽  
Tumor Growth Inhibition ◽  
Cell Cycle Distribution ◽  
Cell Renewal ◽  
Group 3

Abstract Background Group 3 medulloblastoma (MB) is often accompanied by MYC amplification. PLK1 is an oncogenic kinase that controls cell cycle and proliferation and has been preclinically validated as a cancer therapeutic target. Onvansertib (PCM-075) is a novel, orally available PLK1 inhibitor, which shows tumor growth inhibition in various types of cancer. We aim to explore the effect of onvansertib on MYC-driven medulloblastoma as a monotherapy or in combination with radiation. Methods Crisper-Cas9 screen was used to discover essential genes for MB tumor growth. Microarray and immunohistochemistry on pediatric patient samples were performed to examine the expression of PLK1. The effect of onvansertib in vitro was measure by cell viability, colony-forming assays, extreme limiting dilution assay and RNA-Seq. ALDH activity, cell-cycle distribution and apoptosis were analyzed by flow cytometry. DNA damage was assessed by immunofluorescence staining. Medulloblastoma xenografts were generated to explore the monotherapy or radio-sensitizing effect. Results PLK1 is overexpressed in Group 3 MB. The IC50 concentrations of onvansertib in Group 3 MB cell lines were in a low nanomolar range. Onvansertib reduced colony formation, cell proliferation, stem cell renewal and induced G2/M arrest in vitro. Moreover, onvansertib in combination with radiation increased DNA damage and apoptosis compare with radiation treatment alone. The combination radiotherapy resulted in marked tumor regression in xenografts. Conclusions These findings demonstrate the efficacy of a novel PLK1 inhibitor onvansertib in vitro and in xenografts of Group 3 MB, which suggests onvansertib is an effective strategy as monotherapy or in combination with radiotherapy in MB.

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