Zhunussova Aigul, Vitol Elina A, Polyak Boris, Tuleukhanov Sultan, Brooks Ari D, Sensenig Richard, Friedman Gary, Orynbayeva Zulfiya
Department of Surgery, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
Department of Biophysics and Biomedicine, Al-Farabi Kazakh National University, Almaty, Kazakhstan.
PLoS One. 2016 Jun 6;11(6):e0156818. doi: 10.1371/journal.pone.0156818. eCollection 2016.
Non-thermal atmospheric pressure plasma has attracted great interest due to its multiple potential biomedical applications with cancer treatment being among the most urgent. To realize the clinical potential of non-thermal plasma, the exact cellular and molecular mechanisms of plasma effects must be understood. This work aimed at studying the prostate cancer specific mechanisms of non-thermal plasma effects on energy metabolism as a central regulator of cell homeostasis and proliferation. It was found that cancer cells with higher metabolic rate initially are more resistant to plasma treated phosphate-buffered saline (PBS) since the respiratory and calcium sensitive signaling systems were not responsive to plasma exposure. However, dramatic decline of cancer oxidative phosphorylation developed over time resulted in significant progression of cell lethality. The normal prostate cells with low metabolic activity immediately responded to plasma treated PBS by suppression of respiratory functions and sustained elevation of cytosolic calcium. However, over time the normal cells start recovering their mitochondria functions, proliferate and restore the cell population. We found that the non-thermal plasma induced increase in intracellular ROS is of primarily non-mitochondrial origin. The discriminate non-thermal plasma effects hold a promise for clinical cancer intervention.
非热大气压力等离子体因其多种潜在的生物医学应用而备受关注，其中癌症治疗是最迫切的应用之一。为了实现非热等离子体的临床潜力，必须了解等离子体效应的确切细胞和分子机制。这项工作旨在研究非热等离子体对能量代谢的前列腺癌特异性作用机制，能量代谢是细胞稳态和增殖的核心调节因子。研究发现，代谢率较高的癌细胞最初对经等离子体处理的磷酸盐缓冲盐水（PBS）更具抗性，因为呼吸和钙敏感信号系统对等离子体暴露无反应。然而，随着时间的推移，癌细胞氧化磷酸化的显著下降导致细胞杀伤力显著增加。代谢活性低的正常前列腺细胞通过抑制呼吸功能和持续升高胞质钙，立即对经等离子体处理的PBS作出反应。然而，随着时间的推移，正常细胞开始恢复其线粒体功能，增殖并恢复细胞群体。我们发现，非热等离子体诱导的细胞内活性氧增加主要源于非线粒体。非热等离子体的特异性作用为临床癌症干预带来了希望。
