PEGylated-thymoquinone-nanoparticle mediated retardation of breast cancer cell migration by deregulation of cytoskeletal actin polymerization through miR-34a

Bhattacharya, Saurav; Ahir, Manisha; Patra, Prasun; Mukherjee, Sudeshna; Ghosh, Swatilekha; Mazumdar, Minakshi; Chattopadhyay, Sreya; Das, Tanya; Chattopadhyay, Dhrubajyoti; Adhikary, Arghya

doi:10.1016/j.biomaterials.2015.01.007

Cited by 111 publications

(88 citation statements)

References 48 publications

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“…68, 69 2) The alterations of cell junction were reported here, while our previous work was focused on the cytoskeleton proteins after 24 h AuNRs and/or PPTT treatments. 18 3) In addition, super-resolution imaging technique (STORM) revealed more detailed structural information on the effects of our treatment.…”

Section: Resultsmentioning

confidence: 77%

Gold Nanorod Photothermal Therapy Alters Cell Junctions and Actin Network in Inhibiting Cancer Cell Collective Migration

et al. 2018

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Most cancer-related deaths come from metastasis. It was recently discovered that nanoparticles could inhibit cancer cell migration. While most researchers focus on single-cell migration, the effect of nanoparticle treatment on collective cell migration has not been explored. Collective migration occurs commonly in many types of cancer metastasis, where a group of cancer cells move together, which requires the contractility of the cytoskeleton filaments and the connection of neighboring cells by the cell junction proteins. Here, we demonstrate gold nanorods (AuNRs) and the introduction of near-infrared light could inhibit the cancer cell collective migration by altering the actin filaments and cell junctions with significantly triggered phosphorylation changes of essential proteins, using mass spectrometry-based phosphoproteomics. Further observation using super-resolution stochastic optical reconstruction microscopy (STORM) showed the actin cytoskeleton filament bundles were disturbed, which is difficult to differentiate under a normal fluorescence microscope. The decreased expression level of N-Cadherin junctions and morphological changes of tight junction protein zonula occludens 2 (ZO-2) were also observed. All these results indicate possible functions of the AuNRs treatments in regulating and remodeling the actin filaments and cell junction proteins, which contribute to decreasing cancer cell collective migration.

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Section: Resultsmentioning

confidence: 77%

Gold Nanorod Photothermal Therapy Alters Cell Junctions and Actin Network in Inhibiting Cancer Cell Collective Migration

et al. 2018

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“…Similarly, hydrophilic polymeric polyethylene glycol nanoparticles combined with thymoquinone, a major active constituent of black seeds of Nigella sativa, have been found to possess distinct cell migration-retarded effects against breast cancer cells. 26 Interestingly, our study found that CHI nanoparticles themselves also retarded T24 cell migration by ~75%, which could partially explain why CHI nanoparticle aggregation largely strengthens the antimigratory effects of HET on the bladder carcinoma cells. It is noteworthy that gold nanoparticles themselves, particularly gold nanospheres and long gold nanorods with positive potentials, were revealed to have higher capacity to inhibit prostate carcinoma cell migration compared with gold nanoparticles with negative potential.…”

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confidence: 61%

Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

Huang

Kuo

et al. 2016

IJN

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The effects against tumors exerted by marine active compounds have been highlighted and investigated. Polymeric nanoparticles made from biodegradable and biocompatible molecules such as hyaluronan (HA) and chitosan (CHI) are able to aggregate the compounds to enhance their activities against tumor cells and reduce the toxicity on normal cells. Here, we extensively examined the antitumor activities and the mechanisms of HA/CHI nanoparticles-aggregated heteronemin (HET) extracted from the sponge Hippospongia sp. The half-maximal inhibitory concentration (IC 50 ) of pure HET toward T24 bladder carcinoma cells is ~0.28 µg/mL. Pure HET from 0.2 to 0.8 µg/mL and HA nanoparticles-aggregated HET at 0.1 and 0.2 µg/mL significantly reduced T24 cell viability. Compared to pure HET, HA nanoparticles/HET aggregates showed much weaker viability-inhibitory effects on L929 normal fibroblasts. HET dose-dependently suppressed cancer cell migration as HA/CHI nanoparticles-aggregated HET displayed stronger migration-inhibitory effects than pure HET. Flow cytometric analysis showed that pure HET increased early/total apoptosis and JC-1 monomer fluorescence, while HA/CHI nanoparticles-aggregated HET induced higher apoptosis and JC-1 monomer rates than pure HET, suggesting that aggregation of HA nanoparticles offers HET stronger apoptosis-inducing capacity through mitochondrial depolarization. Western blot analysis showed that HA nanoparticles-aggregated HET further increased mitochondrial-associated, caspase-dependent and caspase-independent, as well as endoplasmic reticulum stress-related factors in comparison with pure HET. These data indicated that pure HET possesses cytotoxic, antimigratory, and apoptosis-inducing effects on bladder cancer cells in vitro, and its induction of apoptosis in bladder carcinoma cells is mainly caspase dependent. Moreover, HA nanoparticle aggregation reinforced the cytotoxic, antimigratory, and apoptosis-inducing activities against bladder carcinoma cells and attenuated the viability-inhibitory effects on normal fibroblasts. This aggregation reinforces antibladder carcinoma effects of HET via diverse routes, including mitochondrial-related/caspase-dependent, caspase-independent, and endoplasmic reticulum stress-related pathways. The current data also strongly suggested that HA/CHI nanoparticles-aggregated HET would be a potential treatment for urothelial cancer in vivo.

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“…Previous studies proposed that TQ induces cell cycle arrest and triggers apoptosis of tumor cells through p38, NF-κB and ERK signaling pathways [11, 35, 61–64]. It has been reported that the anti-metastatic effects of TQ are likely to be mediated by the stimulation of miRNA profiles [35, 65–68]. Targeting miRNA and TQ may deliver a new outlook of tumor metastasis suppression by targeting EMT-TFs pathways in different cancer cells [35, 69–71].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion

et al. 2017

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MicroRNA-34a (miR-34a) plays an essential role against tumorigenesis and progression of cancer metastasis. Here, we analyzed the expression, targets and functional effects of miR-34a on epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs), such as TWIST1, SLUG and ZEB1/2, and an EMT-inducing protein NOTCH1 in breast cancer (BC) cell migration and invasion and its correlation with tumorigenesis and clinical outcomes. Expression of miR-34a is downregulated in human metastatic breast cancers (MBC) compared to normal breast tissues and is negatively correlated with clinicopathological features of MBC patients. Ectopic expression of miR-34a in MBC cell-line BT-549 significantly inhibits cell migration and invasion, but exhibits no clear effect on BC cell growth. We found that miR-34a is able to inactivate EMT signaling pathway with mediatory of NOTCH1, TWIST1, and ZEB1 upon 3′-UTR activity in MBC cell lines, but has no inhibitory effects on SLUG and ZEB2. Furthermore, we investigated the synergistic effects of Thymoquinone (TQ) and miR-34a together on the expression of EMT-associated proteins. Results showed that co-delivery of miR-34a and TQ is able to inactivate EMT signaling pathway by directly targeting TWIST1 and ZEB1 in BT-549 cell line, indicating that they might be a promising therapeutic combination against breast cancer metastasis. Epigenetic inactivation of the EMT-TFs/miR-34a pathway can potentially alter the equilibrium of these regulations, facilitating EMT and metastasis in BC. Altogether, our findings suggest that miR-34a alone could serve as a potential therapeutic agent for MBC, and together with TQ, their therapeutic potential is synergistically enhanced.

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PEGylated-thymoquinone-nanoparticle mediated retardation of breast cancer cell migration by deregulation of cytoskeletal actin polymerization through miR-34a

Cited by 111 publications

References 48 publications

Gold Nanorod Photothermal Therapy Alters Cell Junctions and Actin Network in Inhibiting Cancer Cell Collective Migration

Gold Nanorod Photothermal Therapy Alters Cell Junctions and Actin Network in Inhibiting Cancer Cell Collective Migration

Improvement and enhancement of antibladder carcinoma cell effects of heteronemin by the nanosized hyaluronan aggregation

MicroRNA-34a targets epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs) and inhibits breast cancer cell migration and invasion

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