RESUMO
Low Temperature Plasma (LTP) generates reactive oxygen and nitrogen species, causing cell death, similarly to radiation. Radiation resistance results in tumour recurrence, however mechanisms of LTP resistance are unknown. LTP was applied to patient-derived prostate epithelial cells and gene expression assessed. A typical global oxidative response (AP-1 and Nrf2 signalling) was induced, whereas Notch signalling was activated exclusively in progenitor cells. Notch inhibition induced expression of prostatic acid phosphatase (PAP), a marker of prostate epithelial cell differentiation, whilst reducing colony forming ability and preventing tumour formation. Therefore, if LTP is to be progressed as a novel treatment for prostate cancer, combination treatments should be considered in the context of cellular heterogeneity and existence of cell type-specific resistance mechanisms.
Assuntos
Gases em Plasma/uso terapêutico , Neoplasias da Próstata/radioterapia , Tolerância a Radiação/efeitos da radiação , Receptores Notch/genética , Fosfatase Ácida/genética , Morte Celular/efeitos da radiação , Diferenciação Celular/efeitos da radiação , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Células Epiteliais/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Masculino , Fator 2 Relacionado a NF-E2/genética , Gases em Plasma/efeitos adversos , Próstata/patologia , Próstata/efeitos da radiação , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Tolerância a Radiação/genética , Espécies Reativas de Nitrogênio/efeitos da radiação , Espécies Reativas de Oxigênio/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Células-Tronco/efeitos da radiação , Fator de Transcrição AP-1/genéticaRESUMO
The field of plasma medicine has seen substantial advances over the last decade, with applications developed for bacterial sterilisation, wound healing and cancer treatment. Low temperature plasmas (LTPs) are particularly suited for medical purposes since they are operated in the laboratory at atmospheric pressure and room temperature, providing a rich source of reactive oxygen and nitrogen species (RONS). A great deal of research has been conducted into the role of reactive species in both the growth and treatment of cancer, where long-established radio- and chemo-therapies exploit their ability to induce potent cytopathic effects. In addition to producing a plethora of RONS, LTPs can also create strong electroporative fields. From an application perspective, it has been shown that LTPs can be applied precisely to a small target area. On this basis, LTPs have been proposed as a promising future strategy to accurately and effectively control and eradicate tumours. This review aims to evaluate the current state of the literature in the field of plasma oncology and highlight the potential for the use of LTPs in combination therapy. We also present novel data on the effect of LTPs on cancer stem cells, and speculatively outline how LTPs could circumvent treatment resistance encountered with existing therapeutics.
Assuntos
Neoplasias/terapia , Gases em Plasma/uso terapêutico , Animais , Temperatura Baixa , Crioterapia , Humanos , Neoplasias/patologia , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Despite considerable advances in recent years for the focal treatment of localized prostate cancer, high recurrence rates and detrimental side effects are still a cause for concern. In this review, we compare current focal therapies to a potentially novel approach for the treatment of early onset prostate cancer: low temperature plasma. The rapidly evolving plasma technology has the potential to deliver a wide range of promising medical applications via the delivery of plasma-induced reactive oxygen and nitrogen species. Studies assessing the effect of low temperature plasma on cell lines and xenografts have demonstrated DNA damage leading to apoptosis and reduction in cell viability. However, there have been no studies on prostate cancer, which is an obvious candidate for this novel therapy. We present here the potential of low temperature plasma as a focal therapy for prostate cancer.
Assuntos
Temperatura Baixa , Crioterapia , Fotoquimioterapia , Neoplasias da Próstata/terapia , Apoptose/genética , Dano ao DNA , Humanos , Masculino , Neoplasias da Próstata/patologia , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Research in the new field of plasma medicine continues to demonstrate the efficacy of low temperature plasmas for numerous biomedical applications. Responses such as reduction in cell viability and cell death for cancer therapy, cell proliferation for wound healing, and bacterial inactivation have been observed as a result of plasma treatment. In this study we applied low temperature plasma to prostate cancer primary cells and tissue to inflict irreparable DNA damage.
