Veronico Valeria, Morelli Sabrina, Piscioneri Antonella, Gristina Roberto, Casiello Michele, Favia Pietro, Armenise Vincenza, Fracassi Francesco, De Bartolo Loredana, Sardella Eloisa
Department of Chemistry, University of Bari Aldo Moro, via Orabona, 4, 70126 Bari, Italy.
CNR-Institute on Membrane Technology (CNR-ITM), Via Pietro Bucci Cubo, 17/C, 87036 Rende, CS, Italy.
ACS Omega. 2023 Sep 1;8(37):33723-33736. doi: 10.1021/acsomega.3c04061. eCollection 2023 Sep 19.
Water solutions treated by cold atmospheric plasmas (CAPs) currently stand out in the field of cancer treatment as sources of exogenous blends of reactive oxygen and nitrogen species (RONS). It is well known that the balance of RONS inside both eukaryotic and prokaryotic cells is directly involved in physiological as well as pathological pathways. Also, organic molecules including phenols could exert promising anticancer effects, mostly attributed to their pro-oxidant ability in vitro and in vivo to generate RONS like O, HO, and a mixture of potentially cytotoxic compounds. By our vision of combining the efficacy of plasma-produced RONS and the use of organic molecules, we could synergistically attack cancer cells; yet, so far, this combination, to the best of our knowledge, has been completely unexplored. In this study, l-tyrosine, an amino acid with a phenolic side chain, is added to a physiological solution, often used in clinical practice (SIII) to be exposed to plasma. The efficacy of the gas plasma-oxidized SIII solution, containing tyrosine, was evaluated on four cancer cell lines selected from among tumors with poor prognosis (SHSY-5Y, MCF-7, HT-29, and SW-480). The aim was to induce tumor toxicity and trigger apoptosis pathways. The results clearly indicate that the plasma-treated water solution (PTWS) reduced cell viability and oxygen uptake due to an increase in intracellular ROS levels and activation of apoptosis pathways in all investigated cancer cells, which may be related to the activation of the mitochondrial-mediated and p-JNK/caspase-3 signaling pathways. This research offers improved knowledge about the physiological mechanisms underlying cancer treatment and a valid method to set up a prompt, adequate, and effective cancer treatment in the clinic.
冷大气等离子体(CAPs)处理过的水溶液目前作为活性氧和氮物种(RONS)的外源性混合物来源,在癌症治疗领域脱颖而出。众所周知,真核细胞和原核细胞内RONS的平衡直接参与生理以及病理途径。此外,包括酚类在内的有机分子可能发挥有前景的抗癌作用,这主要归因于它们在体外和体内产生如O、HO等RONS以及潜在细胞毒性化合物混合物的促氧化能力。通过我们将等离子体产生的RONS的功效与有机分子的使用相结合的设想,我们可以协同攻击癌细胞;然而,据我们所知,到目前为止,这种组合尚未得到充分探索。在本研究中,将具有酚侧链的氨基酸L-酪氨酸添加到临床实践中常用的生理溶液(SIII)中,使其暴露于等离子体。对从预后不良的肿瘤中选出的四种癌细胞系(SHSY-5Y、MCF-7、HT-29和SW-480)评估了含酪氨酸的气体等离子体氧化SIII溶液的功效。目的是诱导肿瘤毒性并触发凋亡途径。结果清楚地表明,等离子体处理的水溶液(PTWS)降低了细胞活力和氧气摄取,这是由于所有研究的癌细胞中细胞内ROS水平升高以及凋亡途径的激活,这可能与线粒体介导途径和p-JNK/半胱天冬酶-3信号通路的激活有关。这项研究提供了关于癌症治疗潜在生理机制的更多知识,以及一种在临床上建立快速、适当和有效癌症治疗的有效方法。