Plasma for cancer treatment: How can RONS penetrate through the cell membrane? Answers from computer modeling

Bogaerts, Annemie; Yusupov, Maksudbek; Razzokov, Jamoliddin; Paal, Jonas Van der

doi:10.1007/s11705-018-1786-8

Cited by 31 publications

(30 citation statements)

References 72 publications

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“…In contrast, when lower concentrations of cholesterol were present (i.e., cancer cells), the cell membrane was more vulnerable to oxidative stress and it favoured pore formation [48]. The pores generated in the cell membrane facilitated the pass of plasma-generated ROS into the intracellular compartment [67,68], where they could exert further oxidative damage to cells. Our simulation results are in agreement with the literature, as we demonstrate here that RONS present in PT-PBS (e.g., H 2 O 2 , NO 3 − and NO 2 − ions [24,30] oxidize the cell membrane (as can be deduced from the lipid peroxidation experiments, see Figure 6).…”

Section: Resultsmentioning

confidence: 99%

Synergistic Effects of Melittin and Plasma Treatment: A Promising Approach for Cancer Therapy

Shaw

Kumar

Hammerschmid

et al. 2019

Cancers

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Melittin (MEL), a small peptide component of bee venom, has been reported to exhibit anti-cancer effects in vitro and in vivo. However, its clinical applicability is disputed because of its non-specific cytotoxicity and haemolytic activity in high treatment doses. Plasma-treated phosphate buffered saline solution (PT-PBS), a solution rich in reactive oxygen and nitrogen species (RONS) can disrupt the cell membrane integrity and induce cancer cell death through oxidative stress-mediated pathways. Thus, PT-PBS could be used in combination with MEL to facilitate its access into cancer cells and to reduce the required therapeutic dose. The aim of our study is to determine the reduction of the effective dose of MEL required to eliminate cancer cells by its combination with PT-PBS. For this purpose, we have optimised the MEL threshold concentration and tested the combined treatment of MEL and PT-PBS on A375 melanoma and MCF7 breast cancer cells, using in vitro, in ovo and in silico approaches. We investigated the cytotoxic effect of MEL and PT-PBS alone and in combination to reveal their synergistic cytological effects. To support the in vitro and in ovo experiments, we showed by computer simulations that plasma-induced oxidation of the phospholipid bilayer leads to a decrease of the free energy barrier for translocation of MEL in comparison with the non-oxidized bilayer, which also suggests a synergistic effect of MEL with plasma induced oxidation. Overall, our findings suggest that MEL in combination with PT-PBS can be a promising combinational therapy to circumvent the non-specific toxicity of MEL, which may help for clinical applicability in the future.

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Section: Resultsmentioning

confidence: 99%

Synergistic Effects of Melittin and Plasma Treatment: A Promising Approach for Cancer Therapy

Shaw

Kumar

Hammerschmid

et al. 2019

Cancers

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“…In the past few years, nanotechnology combined with CAP technology has exhibited some promising aspects in cancer research by the activation/deactivation of cellular pathways [17]. Additionally, it has been proposed by some research groups that CAP can help in selective cell membrane permeability, which helps in the invasion of CAP-generated direct and indirect RONS species, leading to the intracellular invasion of nanoparticles towards applied sites [18][19][20]. However, at the clinical level, the outcome of the survival of melanoma patients has been very limited due to the targeted mutation in molecular targeted therapy [21].…”

Section: Introductionmentioning

confidence: 99%

Cold Atmospheric Plasma and Silymarin Nanoemulsion Activate Autophagy in Human Melanoma Cells

Adhikari

Ghimire

et al. 2020

IJMS

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Background: Autophagy is reported as a survival or death-promoting pathway that is highly debatable in different kinds of cancer. Here, we examined the co-effect of cold atmospheric plasma (CAP) and silymarin nanoemulsion (SN) treatment on G-361 human melanoma cells via autophagy induction. Methods: The temperature and pH of the media, along with the cell number, were evaluated. The intracellular glucose level and PI3K/mTOR and EGFR downstream pathways were assessed. Autophagy-related genes, related transcriptional factors, and autophagy induction were estimated using confocal microscopy, flow cytometry, and ELISA. Results: CAP treatment increased the temperature and pH of the media, while its combination with SN resulted in a decrease in intracellular ATP with the downregulation of PI3K/AKT/mTOR survival and RAS/MEK transcriptional pathways. Co-treatment blocked downstream paths of survival pathways and reduced PI3K (2 times), mTOR (10 times), EGFR (5 times), HRAS (5 times), and MEK (10 times). CAP and SN co-treated treatment modulates transcriptional factor expressions (ZKSCAN3, TFEB, FOXO1, CRTC2, and CREBBP) and specific genes (BECN-1, AMBRA-1, MAP1LC3A, and SQSTM) related to autophagy induction. Conclusion: CAP and SN together activate autophagy in G-361 cells by activating PI3K/mTOR and EGFR pathways, expressing autophagy-related transcription factors and genes.

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“…On the other hand, because a common treatment of OS is a surgical resection of the tumor, direct treatment can also be applied to treat resection margins to eliminate remaining tumor tissue and allow for more conservative surgery ( Figure 3 A) [ 54 ]. The exposure to electromagnetic fields in direct treatment may lead to an increase in cell permeability or cell membrane disruption, which can improve the in situ uptake of RONS [ 95 , 96 ] and drugs [ 73 , 97 , 98 ]. Moreover, it has been suggested that the destruction of the tumor extracellular matrix (ECM) may improve the response of tumors to chemotherapy or other treatments [ 99 ], reducing the effective doses needed for postoperative regimens.…”

Section: Potential Application Of Cap In Osmentioning

confidence: 99%

Cold Atmospheric Plasma: A New Strategy Based Primarily on Oxidative Stress for Osteosarcoma Therapy

Mateu-Sanz

Tornín

Ginebra

et al. 2021

JCM

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Osteosarcoma is the most common primary bone tumor, and its first line of treatment presents a high failure rate. The 5-year survival for children and teenagers with osteosarcoma is 70% (if diagnosed before it has metastasized) or 20% (if spread at the time of diagnosis), stressing the need for novel therapies. Recently, cold atmospheric plasmas (ionized gases consisting of UV–Vis radiation, electromagnetic fields and a great variety of reactive species) and plasma-treated liquids have been shown to have the potential to selectively eliminate cancer cells in different tumors through an oxidative stress-dependent mechanism. In this work, we review the current state of the art in cold plasma therapy for osteosarcoma. Specifically, we emphasize the mechanisms unveiled thus far regarding the action of plasmas on osteosarcoma. Finally, we review current and potential future approaches, emphasizing the most critical challenges for the development of osteosarcoma therapies based on this emerging technique.

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Plasma for cancer treatment: How can RONS penetrate through the cell membrane? Answers from computer modeling

Cited by 31 publications

References 72 publications

Synergistic Effects of Melittin and Plasma Treatment: A Promising Approach for Cancer Therapy

Synergistic Effects of Melittin and Plasma Treatment: A Promising Approach for Cancer Therapy

Cold Atmospheric Plasma and Silymarin Nanoemulsion Activate Autophagy in Human Melanoma Cells

Cold Atmospheric Plasma: A New Strategy Based Primarily on Oxidative Stress for Osteosarcoma Therapy

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