scholarly journals Integrin-Targeting Dye-Doped PEG-Shell/Silica-Core Nanoparticles Mimicking the Proapoptotic Smac/DIABLO Protein

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1211
Author(s):  
Rossella De Marco ◽  
Enrico Rampazzo ◽  
Junwei Zhao ◽  
Luca Prodi ◽  
Mayra Paolillo ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mitochondrial Protein ◽  
Cell Uptake ◽  
Peptide Ligand ◽  
Integrin Subunit ◽  
Elevated Expression ◽  
Silica Core ◽  
Apoptotic Activity ◽  
Core Nanoparticles

Cancer cells demonstrate elevated expression levels of the inhibitor of apoptosis proteins (IAPs), contributing to tumor cell survival, disease progression, chemo-resistance, and poor prognosis. Smac/DIABLO is a mitochondrial protein that promotes apoptosis by neutralizing members of the IAP family. Herein, we describe the preparation and in vitro validation of a synthetic mimic of Smac/DIABLO, based on fluorescent polyethylene glycol (PEG)-coated silica-core nanoparticles (NPs) carrying a Smac/DIABLO-derived pro-apoptotic peptide and a tumor-homing integrin peptide ligand. At low μM concentration, the NPs showed significant toxicity towards A549, U373, and HeLa cancer cells and modest toxicity towards other integrin-expressing cells, correlated with integrin-mediated cell uptake and consequent highly increased levels of apoptotic activity, without perturbing cells not expressing the α5 integrin subunit.

scholarly journals Glucose Limitation Sensitizes Cancer Cells to Selenite-Induced Cytotoxic Effect via SLC7A11-Mediated Redox Collapse

2021 ◽  
Author(s):  
Hui Chen ◽  
Han Zhang ◽  
Lixing Cao ◽  
Jinling Cui ◽  
Xuan Ma ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Glucose Deprivation ◽  
Therapeutic Window ◽  
Glucose Starvation ◽  
Glucose Limitation ◽  
Elevated Expression ◽  
Xenograft Models

Abstract Background: Combination of fasting with chemotherapy has been drawn an increasing attention because of the encouraging efficacy. SLC7A11 is frequently over-expressed in most of cancer cells, and elevated expression of SLC7A11 renders cancer cells more susceptible to glucose starvation owing to SLC7A11-mediated redox collapse. Selenite is a representative inorganic form of selenium, and is preferentially accumulated in tumors. This selenophilic peculiarity of cancer cells is closely associated with the elevated expression of SLC7A11. Given the established the link among glucose deprivation, SLC7A11, oxidative stress and selenite, we hypothesized that glucose starvation could specifically sensitize cancer cells to selenite-mediated cytotoxic effect. Methods: The cytotoxic effect of combining selenite with glucose starvation on cancer cell was assessed by crystal violet staining and Annexin V/PI staining. Flow cytometry were employed to assess intracellular ROS levels, labile iron pool and lipid peroxidation. Xenograft models were used to test its in vivo antitumor activity. Commercial assay kit, LC-MS, RNA interference and western blot were applied to investigate the mechanism underlying synergistic effect.Results: It showed that cytotoxic effect of selenite on cancer cells, but not on normal cells, was significantly enhanced in response to the combination of selenite and glucose limitation. Furthermore, in vivo therapeutic efficacy of combining selenite with fasting was dramatically improved in xenograft models of lung and colon cancer. Mechanistically, we found that SLC7A11 expression in cancer cells was up-regulated by selenite both in vitro and in vivo. The elevated SLC7A11 led to accumulation of cystine, depletion of NADPH, and inhibition of cystine to cysteine conversion, which in turn boosted selenite-mediated reactive oxygen species (ROS), followed by enhancement of selenite-mediated cytotoxic effect. Conclusion: The findings of the present study provide an effective and practical approach for increasing the therapeutic window of selenite, and imply that combination of selenite with fasting holds promising potential to be developed a clinically useful regimen for treating certain types of cancer.

scholarly journals Improved Fenton Therapy Using Cancer Cell Hydrogen Peroxide

2018 ◽  
Vol 71 (10) ◽  
pp. 826 ◽  
Author(s):  
Hadi Ranji-Burachaloo ◽  
Qiang Fu ◽  
Paul A. Gurr ◽  
Dave E. Dunstan ◽  
Greg G. Qiao
Keyword(s):  
Cell Viability ◽  
Cancer Cells ◽  
Metal Organic Framework ◽  
Cell Uptake ◽  
Hydrodynamic Diameter ◽  
Mass Ratio ◽  
Metal Organic ◽  
Nanoparticle System ◽  
Nih 3T3

Fenton cancer therapy as a new methodology for the treatment of tumour cells is largely restricted owing to the low stability, high aggregation, and poor selectivity of reported nanoparticles. In this study, an improved approach for the selective destruction of cancer cells is reported. Metal–organic framework (MOF) nanoparticles were synthesized and reduced via a hydrothermal method, and then PEGylated through the surface-initiated atom transfer radical polymerization (SI-ATRP) reaction to produce a PEGylated reduced MOF (P@rMOF). The ratio of PEG to nanoparticles was used to optimize the size and aggregation of the nanoparticles, with 2P@rMOF (2 : 1 mass ratio) having the smallest hydrodynamic diameter. The nanoparticles were further conjugated with folic acid for cell targeting. In vitro cell uptake experiments demonstrated that the internalization of 2P@rMOF-FA nanoparticles into cancer cells (HeLa) was almost 3-fold that of normal cells (NIH-3T3). In the presence of 2P@rMOF-FA, the HeLa cell viability decreased dramatically to 22 %, whereas the NIH-3T3 cell viability remained higher than 80 % after 24 h incubation. The selectivity index for 2P@rMOF-FA is 4.48, which is significantly higher than those reported in the literature for similar strategies. This work thus demonstrates the most stable and selective nanoparticle system for the treatment of cancer cells using the cell’s own H2O2.

scholarly journals Potent Anti-Proliferative, Pro-Apoptotic Activity of the Maytenus Royleanus Extract against Prostate Cancer Cells: Evidence in In-Vitro and In-Vivo Models

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0119859 ◽  
Author(s):  
Maria Shabbir ◽  
Deeba N. Syed ◽  
Rahul K. Lall ◽  
Muhammad Rashid Khan ◽  
Hasan Mukhtar
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
In Vivo Models ◽  
Apoptotic Activity

Novel peptide ligand directs liposomes toward EGF‐R high‐expressing cancer cells in vitro and in vivo

2009 ◽  
Vol 23 (5) ◽  
pp. 1396-1404 ◽  
Author(s):  
Shuxian Song ◽  
Dan Liu ◽  
Jinliang Peng ◽  
Hongwei Deng ◽  
Yan Guo ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Peptide Ligand

scholarly journals Quantitative Proteomics Analysis of Berberine-Treated Colon Cancer Cells Reveals Potential Therapy Targets

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 250
Author(s):  
Pengfei Li ◽  
Zhifang Hao ◽  
Huanhuan Liu ◽  
Bojing Zhu ◽  
Liuyi Dang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Ribosomal Proteins ◽  
Regulatory Networks ◽  
Mitochondrial Protein ◽  
Tissue Array ◽  
Colon Cancer Cells ◽  
Hub Proteins

Colon cancer is one of the most lethal malignancies worldwide. Berberine has been found to exert potential anti-colon cancer activity in vitro and in vivo, although the detailed regulatory mechanism is still unclear. This study aims to identify the underlying crucial proteins and regulatory networks associated with berberine treatment of colon cancer by using proteomics as well as publicly available transcriptomics and tissue array data. Proteome profiling of berberine-treated colon cancer cells demonstrated that among 5130 identified proteins, the expression of 865 and 675 proteins were changed in berberine-treated HCT116 and DLD1 cells, respectively. Moreover, 54 differently expressed proteins that overlapped in both cell lines were mainly involved in mitochondrial protein synthesis, calcium mobilization, and metabolism of fat-soluble vitamins. Finally, GTPase ERAL1 and mitochondrial ribosomal proteins including MRPL11, 15, 30, 37, 40, and 52 were identified as hub proteins of berberine-treated colon cancer cells. These proteins have higher transcriptional and translational levels in colon tumor samples than that of colon normal samples, and were significantly down-regulated in berberine-treated colon cancer cells. Genetic dependency analysis showed that silencing the gene expression of seven hub proteins could inhibit the proliferation of colon cancer cells. This study sheds a light for elucidating the berberine-related regulatory signaling pathways in colon cancer, and suggests that ERAL1 and several mitochondrial ribosomal proteins might be promising therapeutic targets for colon cancer.

scholarly journals Hyperbaric Oxygen Enhanced Mitochondria-Targeted Chemotherapy in Bladder Cancer

2020 ◽  
Author(s):  
Chongxing Shen ◽  
Xiaofeng Yue ◽  
Linyong Dai ◽  
Jianwu Wang ◽  
Jinjin Li ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Hyperbaric Oxygen ◽  
Cell Uptake ◽  
Bladder Cancer Cells ◽  
First Time ◽  
Mitochondria Targeting

Abstract Background: Bladder cancer has a high rate of recurrence and drug resistance due to a lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types. In the study, we aimed to investigate the anti-tumor effect of IR-780 combined with hyperbaric oxygen (HBO) on bladder cancer.Methods: Using in vitro cell line data, in vivo model data and clinical data, we tested the ability of IR-780 to selectively accumulate in bladder cancer. We also evaluated the anti-tumor effect of IR-780 combined or not with HBO both in vitro and in vivo, and explored the potential mechanism of its anti-tumor effect. Results: We revealed for the first time that IR-780 selectively accumulated in bladder cancer (bladder cancer cells, xenografts and bladder cancer samples from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. Further study displayed that the combination with HBO could significantly enhance the antitumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial reactive oxygen species (ROS) production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. Conclusions: These data identify for the first time a combination of IR-780 and HBO (IR-780+HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.

scholarly journals A DM1-doped porous gold nanoshell system for NIR accelerated redox-responsive release and triple modal imaging guided photothermal synergistic chemotherapy

2020 ◽  
Author(s):  
Yan Shen ◽  
Yuan Ding ◽  
Jiasheng Tu ◽  
Pengcheng Xu ◽  
Wenqian Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Multimodal Imaging ◽  
Electrostatic Interactions ◽  
Cell Uptake ◽  
Gold Nanoshell ◽  
Porous Gold

Abstract BackgroundAlthough many treatments are available for breast cancer, poor tumor targeting limits the effectiveness of most approaches and a monotherapy will yield satisfactory results difficultly. Furthermore, the lack of accurate diagnostic and tumor monitoring methods also limit the benefits of treatment. This study aimed to design a nanocarrier based on porous gold nanoshell (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER) which can specifically bind to human epidermal receptor-2 (Her-2) over-expressed breast cancer cells and was incorporated with a derivative of the microtubule-targeting drug maytansine (DM1). PGNSs were prepared and then covered by the mPEG, DM1 and HER via the electrostatic interactions and Au-S bonds. The cytotoxicity of DM1-mPEG/HER-PGNSs on SK-BR-3 and MCF-7 cancer cells was evaluated in terms of cell viability and apoptosis analysis. The selective cancer cell uptake and accumulation were studied via ICP-MS and fluorescence imaging in vitro and in vivo. The multimodal imaging and synergistic chemo-photothermal therapeutic efficacy was investigated in breast cancer tumor-bearing mice. Then the molecular mechanism of the nanoparticles in anti-tumor applications were also elucidated.ResultThe as-prepared DM1-mPEG/HER-PGNSs with a size of 78.6 nm displayed excellent colloidal stability, photothermal conversion ability, and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs exhibited selectively uptake by cancer cells in vitro and accumulation to tumor sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs showed enhanced multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumor cell apoptosis via the activation of tubulin, caspase-3 and the HSP70 pathway. Meanwhile, the suppression of M2 macrophages and anti-metastatic functions were observed.ConclusionThese DM1-mPEG/HER-PGNSs would display nanodart-like targeting CT/PA/PT imaging in vivo and powerful tumor inhibition mediated by chemo-thermal combination therapy suggest that these unique gold nanocarriers are potential theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted antitumor drug delivery system to achieve precision nanomedicine for cancer.

scholarly journals Discovering and Characterizing of Survivin Dominant Negative Mutants With Stronger Pro-apoptotic Activity on Cancer Cells and CSCs

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Guo ◽  
Xingyuan Ma ◽  
Yunhui Fu ◽  
Chang Liu ◽  
Qiuli Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Cells ◽  
A549 Cells ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Anti Cancer ◽  
Apoptotic Activity ◽  
Reversal Index ◽  
Negative Mutant

Survivin as a member of the inhibitor of apoptosis proteins (IAPs) family is undetectable in normal cells, but highly expressed in cancer cells and cancer stem cells (CSCs) which makes it an attractive target in cancer therapy. Survivin dominant negative mutants have been reported as competitive inhibitors of endogenous survivin protein in cancer cells. However, there is a lack of systematic comparative studies on which mutants have stronger effect on promoting apoptosis in cancer cells, which will hinder the development of novel anti-cancer drugs. Here, based on the previous study of survivin and its analysis of the relationship between structure and function, we designed and constructed a series of different amino acid mutants from survivin (TmSm34, TmSm48, TmSm84, TmSm34/48, TmSm34/84, and TmSm34/48/84) fused cell-permeable peptide TATm at the N-terminus, and a dominant negative mutant TmSm34/84 with stronger pro-apoptotic activity was selected and evaluated systematically in vitro. The double-site mutant of survivin (TmSm34/84) showed more robust pro-apoptotic activity against A549 cells than others, and could reverse the resistance of A549 CSCs to adriamycin (ADM) (reversal index up to 7.01) by decreasing the expression levels of survivin, P-gp, and Bcl-2 while increasing cleaved caspase-3 in CSCs. This study indicated the selected survivin dominant negative mutant TmSm34/84 is promising to be an excellent candidate for recombinant anti-cancer protein by promoting apoptosis of cancer cells and their stem cells and sensitizing chemotherapeutic drugs.

scholarly journals Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14

2017 ◽  
Vol 44 (3) ◽  
pp. 998-1010 ◽  
Author(s):  
Jiahui Wu ◽  
Xiang Chen ◽  
Qianyi Bao ◽  
Rui Duan ◽  
Yucui Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Genes ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Elevated Expression ◽  
Hoechst Staining

Background/Aims: Osterix (Osx), a key regulator of osteoblast differentiation and bone formation, has been recently reported to be associated with the progression of breast cancer. However, the precise roles of Osx in breast cancer remain unclear. Methods: Drug sensitivity of the cancer cells was assessed using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Target genes were obtained by high-throughput Illumina sequencing and were confirmed in vitro and in vivo. Apoptosis was analysed by Hoechst staining and western blotting. A tissue microarray including 129 samples from breast cancer patients was used for immunohistochemistry (IHC) assays. Results: Overexpression of Osx decreased the chemosensitivity of breast cancer cells, while knockdown of Osx increased the chemosensitivity of breast cancer cells. In particular, we found that the decreased chemosensitivity effect was significantly associated with elevated expression of the polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14). Silencing of GALNT14 in Osx-overexpressed cells restored the decreased chemosensitivity. Conversely, overexpression of GALNT14 in Osx-knockdown cells abrogated the increased chemosensitivity in breast cancer cells. In addition, we revealed that Osx decreased GALNT14-dependent chemosensitivity by enhancing anti-apoptosis. GALNT14 expression exhibited a significant association with breast cancer stages as well as the disease-free survival (DFS) rate. Conclusion: Osx plays an important role in the chemosensitivity and inhibition of Osx expression may represent a therapeutic strategy to enhance the chemosensitivity of breast cancer.

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