Exploiting the TSA connections to overcome apoptosis-resistance

Ranganathan, Padhma

doi:10.4161/cbt.4.4.1779

Cited by 13 publications

(8 citation statements)

References 15 publications

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“…Mishra et al (2001) reported that HDAC inhibitors are able to reduce cell survival in human breast cancer cells through remodeling of the human epidermal growth factor receptor 2 (HER2) promoter and HER2 expression [12]. Trichostatin A (TSA) is one of several inhibitors, which shows a potential therapeutic effect in various types of cancer cells, when combined with radiotherapy or chemotherapy [13,14]. TSA causes apoptosis through the inhibition of cell viability, as well as proliferation and activation of apoptosis-related proteins in a variety of cancer cells, including human gastric, ovarian and small cell lung cancer cells [15,16,17].…”

Section: Introductionmentioning

confidence: 99%

Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells

Zhang

Shen

et al. 2016

IJMS

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Cervical cancer ranks seventh overall among all types of cancer in women. Although several treatments, including radiation, surgery and chemotherapy, are available to eradicate or reduce the size of cancer, many cancers eventually relapse. Thus, it is essential to identify possible alternative therapeutic approaches for cancer. We sought to identify alternative and effective therapeutic approaches, by first synthesizing palladium nanoparticles (PdNPs), using a novel biomolecule called saponin. The synthesized PdNPs were characterized by several analytical techniques. They were significantly spherical in shape, with an average size of 5 nm. Recently, PdNPs gained much interest in various therapies of cancer cells. Similarly, histone deacetylase inhibitors are known to play a vital role in anti-proliferative activity, gene expression, cell cycle arrest, differentiation and apoptosis in various cancer cells. Therefore, we selected trichostatin A (TSA) and PdNPs and studied their combined effect on apoptosis in cervical cancer cells. Cells treated with either TSA or PdNPs showed a dose-dependent effect on cell viability. The combinatorial effect, tested with 50 nM TSA and 50 nMPdNPs, had a more dramatic inhibitory effect on cell viability, than either TSA or PdNPs alone. The combination of TSA and PdNPs had a more pronounced effect on cytotoxicity, oxidative stress, mitochondrial membrane potential (MMP), caspase-3/9 activity and expression of pro- and anti-apoptotic genes. Our data show a strong synergistic interaction between TSA and PdNPs in cervical cancer cells. The combinatorial treatment increased the therapeutic potential and demonstrated relevant targeted therapy for cervical cancer. Furthermore, we provide the first evidence for the combinatory effect and cytotoxicity mechanism of TSA and PdNPs in cervical cancer cells.

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Section: Introductionmentioning

confidence: 99%

Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells

Zhang

Shen

et al. 2016

IJMS

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“…17 Among the various types of HDACIs, trichostatin A (TSA) is an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture and one of the most potent and selective deacetylase (HDAC) inhibitors, which shows a potential therapeutic effect in various types of cancer cells, when combined with radiotherapy or chemotherapy. 18 TSA causes apoptosis through the inhibition of cell viability, as well as proliferation of cells expressing apoptosis-related proteins and activation of those proteins in a variety of cancer cells, including human breast, gastric, ovarian, small-cell lung, and cervical cancer cells. [19][20][21][22][23] TSA is not only a potential inducer of apoptosis but also involved in reprogramming efficiencies of stem cells.…”

Section: Introductionmentioning

confidence: 99%

Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

Zhang¹,

Huang²,

Zhang³

et al. 2017

IJN

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Background Recently, there has been much interest in the field of nanomedicine to improve prevention, diagnosis, and treatment. Combination therapy seems to be most effective when two different molecules that work by different mechanisms are combined at low dose, thereby decreasing the possibility of drug resistance and occurrence of unbearable side effects. Based on this consideration, the study was designed to investigate the combination effect of reduced graphene oxide-silver nanoparticles (rGO-AgNPs) and trichostatin A (TSA) in human ovarian cancer cells (SKOV3). Methods The rGO-AgNPs were synthesized using a biomolecule called lycopene, and the resultant product was characterized by various analytical techniques. The combination effect of rGO-Ag and TSA was investigated in SKOV3 cells using various cellular assays such as cell viability, cytotoxicity, and immunofluorescence analysis. Results AgNPs were uniformly distributed on the surface of graphene sheet with an average size between 10 and 50 nm. rGO-Ag and TSA were found to inhibit cell viability in a dose-dependent manner. The combination of rGO-Ag and TSA at low concentration showed a significant effect on cell viability, and increased cytotoxicity by increasing the level of malondialdehyde and decreasing the level of glutathione, and also causing mitochondrial dysfunction. Furthermore, the combination of rGO-Ag and TSA had a more pronounced effect on DNA fragmentation and double-strand breaks, and eventually induced apoptosis. Conclusion This study is the first to report that the combination of rGO-Ag and TSA can cause potential cytotoxicity and also induce significantly greater cell death compared to either rGO-Ag alone or TSA alone in SKOV3 cells by various mechanisms including reactive oxygen species generation, mitochondrial dysfunction, and DNA damage. Therefore, this combination chemotherapy could be possibly used in advanced cancers that are not suitable for radiation therapy or surgical treatment and facilitate overcoming tumor resistance and disease progression.

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“…Resveratrol was proved to affect ovarian, breast and digestive tract tumors [35][36][37][38]. Trichostatin A, as a histone deacetylase (HDAC) inhibitor, exhibits anticancer effects when used in combination with radiotherapy or chemotherapy [39,40].…”

Section: Discussionmentioning

confidence: 99%

Identification of molecular markers associated with the progression and prognosis of endometrial cancer: a bioinformatic study

Liu

Feng

et al. 2020

Cancer Cell Int

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Background: Endometrial cancer (EC) is one kind of women cancers. Bioinformatic technology could screen out relative genes which made targeted therapy becoming conventionalized. Methods: GSE17025 were downloaded from GEO. The genomic data and clinical data were obtained from TCGA. R software and bioconductor packages were used to identify the DEGs. Clusterprofiler was used for functional analysis. STRING was used to assess PPI information and plug-in MCODE to screen hub modules in Cytoscape. The selected genes were coped with functional analysis. CMap could find EC-related drugs that might have potential effect. Univariate and multivariate Cox proportional hazards regression analyses were performed to predict the risk of each patient. Kaplan-Meier curve analysis could compare the survival time. ROC curve analysis was performed to predict value of the genes. Mutation and survival analysis in TCGA database and UALCAN validation were completed. Immunohistochemistry staining from Human Protein Atlas database. GSEA, ROC curve analysis, Oncomine and qRT-PCR were also performed. Results: Functional analysis showed that the upregulated DEGs were strikingly enriched in chemokine activity, and the down-regulated DEGs in glycosaminoglycan binding. PPI network suggested that NCAPG was the most relevant protein. CMap identified 10 small molecules as possible drugs to treat EC. Cox analysis showed that BCHE, MAL and ASPM were correlated with EC prognosis. TCGA dataset analysis showed significantly mutated BHCE positively related to EC prognosis. MAL and ASPM were further validated in UALCAN. All the results demonstrated that the two genes might promote EC progression. The profile of ASPM was confirmed by the results from immunohistochemistry. ROC curve demonstrated that the mRNA levels of two genes exhibited difference between normal and tumor tissues, indicating their diagnostic efficiency. qRT-PCR results supported the above results. Oncomine results showed that DNA copy number variation of MAL was significantly higher in different EC subtypes than in healthy tissues. GSEA suggested that the two genes played crucial roles in cell cycle. Conclusion: BCHE, MAL and ASPM are tumor-related genes and can be used as potential biomarkers in EC treatment.

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Exploiting the TSA connections to overcome apoptosis-resistance

Cited by 13 publications

References 15 publications

Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells

Trichostatin A Enhances the Apoptotic Potential of Palladium Nanoparticles in Human Cervical Cancer Cells

Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

Identification of molecular markers associated with the progression and prognosis of endometrial cancer: a bioinformatic study

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