Cold Atmospheric Plasma, a Novel Approach against Bladder Cancer, with Higher Sensitivity for the High-Grade Cell Line

Tavares-da-Silva, Edgar; Pereira, Eurico; Pires, Ana Salomé; Neves, Rita; Braz-Guilherme, Catarina; Marques, Inês; Abrantes, Ana Margarida; Gonçalves, Ana Cristina; Caramelo, Francisco; Silva-Teixeira, R.; Mendes, Fernando; Figueiredo, Arnaldo; Botelho, Maria Filomena

doi:10.3390/biology10010041

Cited by 17 publications

(13 citation statements)

References 73 publications

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“…Analysis of apoptosis-related genes, including BAX, BCL2, and CASP3, and also BAX/BCL2 ratio indicated CAP induces apoptotic pathway selectivity in tumor cells. Our results are in line with other studies that reported the effect of CAP on cytotoxicity and apoptosis in tumor cell lines [5,6,8,40,[43][44][45][46][47][48]. Other studies proved evidences that CUR has a cytotoxic effect and induces apoptosis in cancer cell lines [49][50][51][52][53][54][55][56].…”

Section: Discussionsupporting

confidence: 91%

Combined Effect of Cold Atmospheric Plasma and Curcumin in Melanoma Cancer

Yazdani

Mehrabanjoubani

Rafiei

et al. 2021

BioMed Research International

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Curcumin (CUR) has interesting properties to cure cancer. Cold atmospheric plasma (CAP) is also an emerging biomedical technique that has great potential for cancer treatment. Therefore, the combined effect of CAP and CUR on inducing cytotoxicity and apoptosis of melanoma cancer cells might be promising. Here, we investigated the combined effects of CAP and CUR on cytotoxicity and apoptosis in B16-F10 melanoma cancer cells compared to L929 normal cells using MTT method, acridine orange/ethidium bromide fluorescence microscopic assay, and Annexin V/PI flow cytometry. In addition, the activation of apoptosis pathways was evaluated using BCL2, BAX, and Caspase-3 (CASP3) gene expression and ratio of BAX to BCL2 (BAX/BCL2). Finally, in silico study was performed to suggest the molecular mechanism of this combination therapy on melanoma cancer. Results showed that although combination therapy with CUR and CAP has cytotoxic and apoptotic effects on cancer cells, it did not improve apoptosis rate in melanoma B16-F10 cancer cells compared to monotherapy with CAP or CUR. In addition, evaluation of gene expression in cancer cell line confirmed that CUR and CAP concomitant treatment did not enhance the expression of apoptotic genes. In silico analysis of docked model suggested that CUR blocks aquaporin- (AQP-) 1 channel and prevents penetration of CAP-induced ROS into the cells. In conclusion, combination therapy with CAP and CUR does not improve the anticancer effect of each alone.

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Section: Discussionsupporting

confidence: 91%

Combined Effect of Cold Atmospheric Plasma and Curcumin in Melanoma Cancer

Yazdani

Mehrabanjoubani

Rafiei

et al. 2021

BioMed Research International

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“…In addition to the direct CAP strategy, CAP activity can also be transferred to liquids (i.e., plasma activated medium (PAM)), adding flexibility to the application of plasma therapy [4][5][6]. PAM, produced by activating culture medium with CAP, has been found to selectively cause a significant reduction in the viability of cancer cells, including breast cancer [7], bladder cancer [8], osteosarcoma [9], and skin cancer [10] cells.…”

Section: Introductionmentioning

confidence: 99%

Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems

Wang

Zhou

Thomas

et al. 2021

Cancers

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Cold atmospheric plasma (CAP) has emerged as a highly selective anticancer agent, most recently in the form of plasma-activated medium (PAM). Since epithelial–mesenchymal transition (EMT) has been implicated in resistance to various cancer therapies, we assessed whether EMT status is associated with PAM response. Mesenchymal breast cancer cell lines, as well as the mesenchymal variant in an isogenic EMT/MET human breast cancer cell system (PMC42-ET/LA), were more sensitive to PAM treatment than their epithelial counterparts, contrary to their responses to other therapies. The same trend was seen in luminal muscle-invasive bladder cancer model (TSU-Pr1/B1/B2) and the non-muscle-invasive basal 5637 bladder cancer cell line. Three-dimensional spheroid cultures of the bladder cancer cell lines were less sensitive to the PAM treatment compared to their two-dimensional counterparts; however, incrementally better responses were again seen in more mesenchymally-shifted cell lines. This study provides evidence that PAM preferentially inhibits mesenchymally-shifted carcinoma cells, which have been associated with resistance to other therapies. Thus, PAM may represent a novel treatment that can selectively inhibit triple-negative breast cancers and a subset of aggressive bladder cancers, which tend to be more mesenchymal. Our approach may potentially be utilized for other aggressive cancers exhibiting EMT and opens new opportunities for CAP and PAM as a promising new onco-therapy.

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“…The cold atmospheric plasma (CAP) operated at ambient temperature has attracted great interest in biomedical fields such as drug delivery and cancer therapy [23,24]. As one of common configurations, a plasma jet containing a high-voltage electrode and carrier gas is used to generate CAP for biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

Carrier-Free Cellular Transport of CRISPR/Cas9 Ribonucleoprotein for Genome Editing by Cold Atmospheric Plasma

Cui

Jiang

Zhou

et al. 2021

Biology

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A carrier-free CRISPR/Cas9 ribonucleoprotein delivery strategy for genome editing mediated by a cold atmospheric plasma (CAP) is described. The CAP is promising in many biomedical applications due to efficient production of bioactive ionized species. The MCF-7 cancer cells after CAP exposure exhibit increased extracellular reactive oxygen and nitrogen species (RONS) and altered membrane potential and permeability. Hence, transmembrane transport of Ca2+ into the cells increases and accelerates ATP hydrolysis, resulting in enhanced ATP-dependent endocytosis. Afterwards, the increased Ca2+ and ATP contents promote the release of cargo into cytoplasm due to the enhanced endosomal escape. The increased membrane permeability also facilitates passive diffusion of foreign species across the membrane into the cytosol. After CAP exposure, the MCF-7 cells incubated with Cas9 ribonucleoprotein (Cas9-sgRNA complex, Cas9sg) with a size of about 15 nm show 88.9% uptake efficiency and 65.9% nuclear import efficiency via passive diffusion and ATP-dependent endocytosis pathways. The efficient transportation of active Cas9sg after the CAP treatment leads to 21.7% and 30.2% indel efficiencies in HEK293T and MCF-7 cells, respectively. This CAP-mediated transportation process provides a simple and robust alternative for the delivery of active CRISPR/Cas9 ribonucleoprotein. Additionally, the technique can be extended to other macro-biomolecules and nanomaterials to cater to different biomedical applications.

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Cold Atmospheric Plasma, a Novel Approach against Bladder Cancer, with Higher Sensitivity for the High-Grade Cell Line

Cited by 17 publications

References 73 publications

Combined Effect of Cold Atmospheric Plasma and Curcumin in Melanoma Cancer

Combined Effect of Cold Atmospheric Plasma and Curcumin in Melanoma Cancer

Epithelial-to-Mesenchymal Transition Enhances Cancer Cell Sensitivity to Cytotoxic Effects of Cold Atmospheric Plasmas in Breast and Bladder Cancer Systems

Carrier-Free Cellular Transport of CRISPR/Cas9 Ribonucleoprotein for Genome Editing by Cold Atmospheric Plasma

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