Cold Atmospheric Plasma: A New Strategy Based Primarily on Oxidative Stress for Osteosarcoma Therapy
Abstract
:1. Background
2. Current Treatment in OS
2.1. Surgery
2.2. Chemotherapy
2.3. Radiotherapy
2.4. Other Therapeutic Options
3. CAP for Cancer Therapy
3.1. Application Methods of Cold Atmospheric Plasma (CAP)
3.2. Anti-Cancer Mechanism of CAP
3.3. Advantages of Using CAP
4. Potential Application of CAP in OS
5. In Vitro Effects of CAP in OS
5.1. Direct Treatment in OS
5.2. Indirect Treatment in OS
6. Challenges of CAP for OS Therapy
6.1. Bone Microenvironment in OS
6.2. Tumor Heterogeneity in OS
6.2.1. Oncogenes in OS
6.2.2. How Could CAP Affect Intracellular Signaling in OS?
6.2.3. Cancer Stem Cells in OS
6.2.4. How Could CAP-Induced Oxidative Stress Affect CSCs in OS?
7. Future Trends
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ALDH | Aldehyde dehydrogenase |
CAP | Cold atmospheric plasma |
CAF | Cancer associated fibroblast |
CSC | Cancer stem cell |
ECM | Extra-cellular matrix |
HSP | Heat-shock protein |
IL | Interleukin |
MSC | Mesenchymal stem cell |
OS | Osteosarcoma |
pRB | Retinoblastoma |
RNS | Reactive nitrogen species |
RONS | Reactive oxygen and nitrogen species |
ROS | Reactive oxygen species |
UV | Ultraviolet |
VEGF | Vascular endothelial growth factor |
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BASIS | ADVANTAGES | DISADVANTAGES | |
---|---|---|---|
SURGERY | Limb amputation; Surgical resection of tumor tissue | ↑ Tumor remission and survival in non-metastatic OS patients. | ↑ Tumor residues, relapse and limb disfunction. ↓ Effectiveness in metastatic OS patients. |
CHEMO- THERAPY | Methotrexate, doxorubicin and cisplatin: inhibits DNA synthesis; Doxorubicin and cisplatin: Free radical production | ↓ Tumor growth; Tumor remission facilitates surgical resection; Eradicates tumor remnants and distal metastasis. | Drug resistance in many patients; Crystal nephropathy; Systemic oxidative stress: hepatotoxicity and cardiotoxicity; Hepatotoxicity, cardiotoxicity, altered bone remodeling function, side effects.any side effects. |
RADIOTHERAPY | Radiation-induced DNA damage; Production of hydroxyl radicals (·OH). | To control of resection margins; Local control of OS tumors that cannot be properly resected. | ↓ Response of OS tumors and a need for ↑ doses; Detrimental effect on normal tissue; Systemic oxidative stress and cytotoxicity; Risk of a radiation-induced secondary tumor. |
IMMUNOTHERAPY | Use of components of the immune system to increase the immune response against cancer cells. | ↓ Side effects than chemo- and radiotherapies and risk of tumor relapse. | ↑ Capabilities of OS to ignore immune system; Autoimmune responses. |
TARGETED THERAPIES | Use of different kinds of inhibitors of critical proto-oncogenes. | Targeted for OS cells; Free of systemic effects. | ↑ Difficulty to identify relevant proto-oncogenes in OS. |
Cell Lines | CAP Device | Cell Response | Refs |
---|---|---|---|
DIRECT CAP TREATMENT→ floating cultures except α | |||
SaOS-2, hMSCs hOBs α | He APPJ * | Cytotoxicity of cancer cells to CAP rather than healthy bone cells. | [112] |
U2-OS, 3T3 | Maxium® CAP Coagulator 1000 kINPen MED | Differential ↓ in proliferation depending on the plasma jet. | [113] |
U2-OS, MNNG/HOS | kINPen MED MiniJet-R | Plasma jet-dependent response; ↓ cell proliferation; activation of caspase-3/7. | [114] |
kINPen MED | ↓ Cell proliferation; p53 phosphorylation; DNA condensation and nuclear degradation. | [115] | |
↓ Cell proliferation and peroxiredoxin expression; NAC-mediated reduction of CAP cytotoxicity. | [116] | ||
Cell line-dependent chemokine and cytokine modulation. | [117] | ||
↑ Cell membrane permeability. | [118] | ||
↓ Cell proliferation and cell membrane permeability; apoptotic cell death. | [119] | ||
INDIRECT CAP TREATMENT (PLASMA-TREATED LIQUIDS) adherent cultures except β | |||
HOS, SaOS-2, 143B | DBD * | Mitochondrial network aberration, ↑ autophagy. | [120] |
HOS, SaOS-2, 143B, hFOB, LM8, K7M3, MC-3T3 | Cytotoxic effect in transformed cells; mitochondrial network aberration; caspase-independent cell death; cell membrane depolarization; Ca2+ homeostasis disruption. | [121] | |
SaOS-2, hMSCs, hOBs | He APPJ | ↑ Cytotoxicity of CAP to cancer cells than healthy bone cells and apoptosis; ↓ focal adhesions. | [112] |
SaOS-2, hBM-MSCs | Selective cytotoxic effects depending on H2O2 generated and the presence of pyruvate, ↑ DNA damage and apoptosis, phospho-kinase alterations. | [104] | |
SaOS-2, MG-63, U2-OS, hBM-MSCs | He APPJ kINPen IND | Selective cell death depending on plasma jet and RONS concentration, induction of intracellular ROS increase, DNA damage and apoptosis between healthy and cancer cells. | [122] |
Tumors produced from MOS-J β | He APPJ | ↓ Proliferating cells and viability. | [122] |
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Mateu-Sanz, M.; Tornín, J.; Ginebra, M.-P.; Canal, C. Cold Atmospheric Plasma: A New Strategy Based Primarily on Oxidative Stress for Osteosarcoma Therapy. J. Clin. Med. 2021, 10, 893. https://doi.org/10.3390/jcm10040893
Mateu-Sanz M, Tornín J, Ginebra M-P, Canal C. Cold Atmospheric Plasma: A New Strategy Based Primarily on Oxidative Stress for Osteosarcoma Therapy. Journal of Clinical Medicine. 2021; 10(4):893. https://doi.org/10.3390/jcm10040893
Chicago/Turabian StyleMateu-Sanz, Miguel, Juan Tornín, Maria-Pau Ginebra, and Cristina Canal. 2021. "Cold Atmospheric Plasma: A New Strategy Based Primarily on Oxidative Stress for Osteosarcoma Therapy" Journal of Clinical Medicine 10, no. 4: 893. https://doi.org/10.3390/jcm10040893