Cold Atmospheric Plasma Attenuates Breast Cancer Cell Growth Through Regulation of Cell Microenvironment Effectors
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ABSTRACT:
SUBMITTER: Aggelopoulos C
PROVIDER: S-EPMC8801750 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionCold plasma is a partially ionized gas generated by an electric field at atmospheric pressure that was initially used in medicine for decontamination and sterilization of inert surfaces. There is currently growing interest in using cold plasma for more direct medical applications, mainly due to the possibility of tuning it to obtain selective biological effects in absence of toxicity for surrounding normal tissues,. While the therapeutic potential of cold plasma in chronic wound, blood coagulation, and cancer treatment is beginning to be documented, information on plasma/cell interaction is so far limited and controversial.Methods and resultsUsing normal primary human fibroblast cultures isolated from oral tissue, we sought to decipher the effects on cell behavior of a proprietary cold plasma device generating guided ionization waves carried by helium. In this model, cold plasma treatment induces a predominantly necrotic cell death. Interestingly, death is not triggered by a direct interaction of the cold plasma with cells, but rather via a transient modification in the microenvironment. We show that modification of the microenvironment redox status suppresses treatment toxicity and protects cells from death. Moreover, necrosis is not accidental and seems to be an active response to an environmental cue, as its execution can be inhibited to rescue cells.ConclusionThese observations will need to be taken into account when studying in vitro plasma/cell interaction and may have implications for the design and future evaluation of the efficacy and safety of this new treatment strategy.
| S-EPMC4537210 | biostudies-literature
Project description:Nano-based drug delivery devices allowing for effective and sustained targeted delivery of therapeutic agents to solid tumors have revolutionized cancer treatment. As an emerging biomedical technique, cold atmospheric plasma (CAP), an ionized non-thermal gas mixture composed of various reactive oxygen species, reactive nitrogen species, and UV photons, shows great potential for cancer treatment. Here we seek to develop a new dual cancer therapeutic method by integrating promising CAP and novel drug loaded core-shell nanoparticles and evaluate its underlying mechanism for targeted breast cancer treatment. For this purpose, core-shell nanoparticles were synthesized via co-axial electrospraying. Biocompatible poly (lactic-co-glycolic acid) was selected as the polymer shell to encapsulate anti-cancer therapeutics. Results demonstrated uniform size distribution and high drug encapsulation efficacy of the electrosprayed nanoparticles. Cell studies demonstrated the effectiveness of drug loaded nanoparticles and CAP for synergistic inhibition of breast cancer cell growth when compared to each treatment separately. Importantly, we found CAP induced down-regulation of metastasis related gene expression (VEGF, MTDH, MMP9, and MMP2) as well as facilitated drug loaded nanoparticle uptake which may aid in minimizing drug resistance-a major problem in chemotherapy. Thus, the integration of CAP and drug encapsulated nanoparticles provides a promising tool for the development of a new cancer treatment strategy.
| S-EPMC4768177 | biostudies-other
Project description:Paclitaxel is a widely used therapeutic chemical for breast cancer treatment, however, cancer recurrence remains obstacle for improved prognosis of cancer patients. In the current study, cold atmospheric plasma (CAP) was examined for its potential use to overcome the drug resistance, which mainly comprised of reactive oxygen and nitrogen species. After developing a paclitaxel (Tx)-resistant MCF-7 (MCF-7/TxR) breast cancer cell, CAP was applied to the cells and its effect on recovery of drug sensitivity was examined in cellular as well as molecular aspect. The MCF-7/TxR cells restored sensitivity against Tx up to 70% by CAP. Comparison of genome-wide expression profiles between the Tx resistance cell and its CAP-treated cell identified 86 genes that commonly appeared with significant change. Notably, 48 genes including DAGLA and CEACAM1, which are known to contribute to the acquisition of Tx resistance, showed opposite expression in the two cellular status. The protein expression level of selected genes, DAGLA and CEACAM1, was recovered to that of their parental cell by CAP. Furthermore, the dysregulation of DAGLA and CEACAM1 in MCF-7/TxR alleviated the drug sensitivity recovery effect of CAP. Taken together, CAP inhibited the growth of Tx-resistant MCF-7 cancer cells and recovered Tx sensitivity by resetting expression of multiple drug resistance–related genes. These findings may contribute to extending the application of CAP to the treatment of Tx-resistant cancer.
2020-01-24 | GSE131479 | GEO
Project description:Cold atmospheric plasma (CAP), a technology based on quasi-neutral ionized gas at low temperatures, is currently being evaluated as a new highly selective alternative addition to existing cancer therapies. Here, we present a first attempt to identify the mechanism of CAP action. CAP induced a robust ~2-fold G2/M increase in two different types of cancer cells with different degrees of tumorigenicity. We hypothesize that the increased sensitivity of cancer cells to CAP treatment is caused by differences in the distribution of cancer cells and normal cells within the cell cycle. The expression of γH2A.X (pSer139), an oxidative stress reporter indicating S-phase damage, is enhanced specifically within CAP treated cells in the S phase of the cell cycle. Together with a significant decrease in EdU-incorporation after CAP, these data suggest that tumorigenic cancer cells are more susceptible to CAP treatment.
| S-EPMC3434394 | biostudies-other
Project description:The selective in vitro anti-tumor mechanisms of cold atmospheric plasma (CAP) and plasma-activated media (PAM) follow a sequential multi-step process. The first step involves the formation of primary singlet oxygen (1O2) through the complex interaction between NO2- and H2O2. 1O2 then inactivates some membrane-associated catalase molecules on at least a few tumor cells. With some molecules of their protective catalase inactivated, these tumor cells allow locally surviving cell-derived, extracellular H2O2 and ONOO─ to form secondary 1O2. These species continue to inactivate catalase on the originally triggered cells and on adjacent cells. At the site of inactivated catalase, cell-generated H2O2 enters the cell via aquaporins, depletes glutathione and thus abrogates the cell's protection towards lipid peroxidation. Optimal inactivation of catalase then allows efficient apoptosis induction through the HOCl signaling pathway that is finalized by lipid peroxidation. An identical CAP exposure did not result in apoptosis for nonmalignant cells. A key conclusion from these experiments is that tumor cell-generated RONS play the major role in inactivating protective catalase, depleting glutathione and establishing apoptosis-inducing RONS signaling. CAP or PAM exposure only trigger this response by initially inactivating a small percentage of protective membrane associated catalase molecules on tumor cells.
| S-EPMC6775051 | biostudies-literature
Project description:genome-wide expression profiling of MCF-7, MCF-7/TamR and CAP-treated MCF-7/TamR cell. In result, cold atmospheric plasma re-sensitizes the Tamoxifen-resistant MCF-7 (MCF-7/TamR) breast cancer cell to the drug.
2017-07-12 | GSE95208 | GEO
Project description:Paclitaxel is a widely used therapeutic chemical for breast cancer treatment, however, cancer recurrence remains obstacle for improved prognosis of cancer patients. In the current study, cold atmospheric plasma (CAP) was examined for its potential use to overcome the drug resistance, which mainly comprised of reactive oxygen and nitrogen species. After developing a paclitaxel (Tx)-resistant MCF-7 (MCF-7/TxR) breast cancer cell, CAP was applied to the cells and its effect on recovery of drug sensitivity was examined in cellular as well as molecular aspect. The MCF-7/TxR cells restored sensitivity against Tx up to 70% by CAP. Comparison of genome-wide expression profiles between the Tx resistance cell and its CAP-treated cell identified 86 genes that commonly appeared with significant change. Notably, 48 genes including DAGLA and CEACAM1, which are known to contribute to the acquisition of Tx resistance, showed opposite expression in the two cellular status. The protein expression level of selected genes, DAGLA and CEACAM1, was recovered to that of their parental cell by CAP. Furthermore, the dysregulation of DAGLA and CEACAM1 in MCF-7/TxR alleviated the drug sensitivity recovery effect of CAP. Taken together, CAP inhibited the growth of Tx-resistant MCF-7 cancer cells and recovered Tx sensitivity by resetting expression of multiple drug resistance–related genes. These findings may contribute to extending the application of CAP to the treatment of Tx-resistant cancer.
2020-01-24 | GSE131478 | GEO
Project description:Cold atmospheric plasma (CAP) has attracted much attention in the fields of biotechnology and medicine owing to its potential utility in clinical applications. Recently accumulating evidence has demonstrated that CAP influences protein structures. However, there remain open questions regarding the molecular mechanisms behind the CAP-induced structural perturbations of biomacromolecules. Here, we investigated the potential effects of CAP irradiation of amyloid β (Aβ), an amyloidogenic protein associated with Alzheimer's disease. Using nuclear magnetic resonance spectroscopy, we observed gradual spectral changes in Aβ after a 10 s CAP pretreatment, which also suppressed its fibril formation, as revealed by thioflavin T assay. As per mass spectrometric analyses, these effects were attributed to selective oxidation of the methionine residue (Met) at position 35. Interestingly, this modification occurred when Aβ was dissolved into a pre-irradiated buffer, indicating that some reactive species oxidize the Met residue. Our results strongly suggest that the H2O2 generated in the solution by CAP irradiation is responsible for Met oxidation, which inhibits Aβ amyloid formation. The findings of the present study provide fundamental insights into plasma biology, giving clues for developing novel applications of CAP.
| S-EPMC8003251 | biostudies-literature
Project description:Hydrogen peroxide (H2O2) is an important signaling molecule in cancer cells. However, the significant secretion of H2O2 by cancer cells have been rarely observed. Cold atmospheric plasma (CAP) is a near room temperature ionized gas composed of neutral particles, charged particles, reactive species, and electrons. Here, we first demonstrated that breast cancer cells and pancreatic adenocarcinoma cells generated micromolar level H2O2 during just 1 min of direct CAP treatment on these cells. The cell-based H2O2 generation is affected by the medium volume, the cell confluence, as well as the discharge voltage. The application of cold atmospheric plasma (CAP) in cancer treatment has been intensively investigated over the past decade. Several cellular responses to CAP treatment have been observed including the consumption of the CAP-originated reactive species, the rise of intracellular reactive oxygen species, the damage on DNA and mitochondria, as well as the activation of apoptotic events. This is a new previously unknown cellular response to CAP, which provides a new prospective to understand the interaction between CAP and cells in vitro and in vivo. The short-lived reactive species in CAP may activate cells in vivo to generate long-lived reactive species such as H2O2, which may trigger immune attack on tumorous tissues via the H2O2-mediated lymphocyte activation.
| S-EPMC5589829 | biostudies-literature
Project description:Cold Atmospheric Plasma (CAP) is an ionized gas with a near room temperature. CAP is a controllable source for reactive species, neutral particles, electromagnetic field and UV radiation. CAP showed the promising application in cancer treatment through the demonstration in vitro and in vivo. In this study, we first demonstrate the existence of an activation state on the CAP-treated cancer cells, which drastically decreases the threshold of cell vulnerability to the cytotoxicity of the CAP-originated reactive species such as H2O2 and NO2-. The cytotoxicity of CAP treatment is still dependent on the CAP-originated reactive species. The activation state of cancer cells will not cause noticeable cytotoxicity. This activation is an instantaneous process, started even just 2?s after the CAP treatment begins. The noticeable activation on the cancer cells starts 10-20?s during the CAP treatment. In contrast, the de-sensitization of activation takes 5 hours after the CAP treatment. The CAP-based cell activation explains the mechanism by which direct CAP treatment causes a much stronger cytotoxicity over the cancer cells compared with an indirect CAP treatment do, which is a key to understand what the effect of CAP on cancer cells.
| S-EPMC6194007 | biostudies-other