pH-Selective Reactions to Selectively Reduce Cancer Cell Proliferation: Effect of CaS Nanostructures in Human Skin Melanoma and Benign Fibroblasts.
pH-Selective Reactions to Selectively Reduce Cancer Cell Proliferation: Effect of CaS Nanostructures in Human Skin Melanoma and Benign Fibroblasts.
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DOI：
10.3390/biochem3010002
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发表时间：
2023-03
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酸性细胞外pH值（pHe）是许多癌症的特征，与大多数良性细胞中发现的生理性pHe相反。这种pH值的差异为设计和工程化学物质提供了独特的机会，这些化学物质可用于癌细胞细胞外液中的pH选择反应。报告了暴露于CaS分散体的人类皮肤黑色素瘤和相应的成纤维细胞的生存能力。黑色素瘤细胞活力随着CaS分散体浓度的降低而降低，在3%时达到57%，这一数值很容易与黑色素瘤对照实验区分开来。相比之下，良性成纤维细胞的活力在实验误差范围内几乎保持不变。CaS分散体促进了血管蛋白在细胞质液中的脱位，结果与黑色素瘤细胞中改善的局灶黏着激酶（FAK）调节一致。热力学方面的考虑与质子存在下CaS的形成是一致的。在固体CaS和酸性水溶液的独立实验中验证了热力学预测。在280 ~ 330 K的温度范围内，反应的活化能为（30±10）kJ/mol。采用总吉布斯能量最小化方法来建立硫化物的分布-包括气相和水相-从CaS解离作为pH值的函数，以模拟生理相关的pH值。理论计算表明，部分质子化的CaS在溶液中可以保持稳定，直到硫原子与两个氢原子结合，形成Ca2+和，Ca2+和可以溶剂化和/或释放到气相。我们的结果与CaS在黑色素瘤细胞胞外液中选择性分离的模型一致。这些结果在CaS分散体在癌症治疗中的潜在生物医学应用的背景下进行了讨论。
An acidic extracellular pH value (pHe) is characteristic of many cancers, in contrast to the physiologic pHe found in most benign cells. This difference in pH offers a unique opportunity to design and engineer chemicals that can be employed for pH-selective reactions in the extracellular fluid of cancer cells. The viability of human skin melanoma and corresponding fibroblasts exposed to CaS dispersions is reported. The viability of melanoma cells decreases with CaS dispersion concentration and reaches 57% at 3%, a value easily distinguishable from melanoma control experiments. In contrast, the viability of benign fibroblasts remains nearly constant within experimental error over the range of dispersion concentrations studied. The CaS dispersions facilitate vinculin delocalization in the cytoplasmic fluid, a result consistent with improved focal adhesion kinase (FAK) regulation in melanoma cells. Thermodynamic considerations are consistent with the formation of from CaS in the presence of protons. The thermodynamic prediction is verified in independent experiments with solid CaS and acidic aqueous solutions. The amount of formed decreases with pH. An activation energy for the process of (30 ± 10) kJ/mol in the temperature range of 280 to 330 K is estimated from initial rate measurements as a function of temperature. The total Gibbs energy minimization approach was employed to establish the distribution of sulfides—including in the gas and aqueous phases—from the dissociation of CaS as a function of pH to mimic physiologically relevant pH values. Theoretical calculations suggest that partially protonated CaS in solution can be stable until the sulfur atom bonds to two hydrogen atoms, resulting in the formation of Ca2+ and , which can be solvated and/or released to the gas phase. Our results are consistent with a model in which CaS is dissociated in the extracellular fluid of melanoma cells selectively. The results are discussed in the context of the potential biomedical applications of CaS dispersions in cancer therapies.