Kwon Youngjoo
Department of Food Science and Engineering, Ewha Womans University, Seoul 03760, Korea.
Antioxidants (Basel). 2021 Jan 24;10(2):169. doi: 10.3390/antiox10020169.
N-acetylcysteine (NAC) is a widely used antioxidant with therapeutic potential. However, the cancer-promoting effect of NAC observed in some preclinical studies has raised concerns regarding its clinical use. Reactive oxygen species (ROS) can mediate signaling that results in both cancer-promoting and cancer-suppressing effects. The beneficial effect of NAC may depend on whether the type of cancer relies on ROS signaling for its survival and metastasis. Triple-negative breast cancer (TNBC) has aggressive phenotypes and is currently treated with standard chemotherapy as the main systemic treatment option. Particularly, basal-like TNBC cells characterized by inactivated and mutated produce high ROS levels and rely on ROS signaling for their survival and malignant progression. In addition, the high ROS levels in TNBC cells can mediate the interplay between cancer cells and the tissue microenvironment (TME) to trigger the recruitment and conversion of stromal cells and induce hypoxic responses, thus leading to the creation of cancer-supportive TMEs and increased cancer aggressiveness. However, NAC treatment effectively reduces the ROS production and ROS-mediated signaling that contribute to cell survival, metastasis, and drug resistance in TNBC cells. Therefore, the inclusion of NAC in standard chemotherapy could probably provide additional benefits for TNBC patients.
N-乙酰半胱氨酸（NAC）是一种具有治疗潜力且被广泛使用的抗氧化剂。然而，一些临床前研究中观察到的NAC的促癌作用引发了对其临床应用的担忧。活性氧（ROS）可介导产生促癌和抑癌作用的信号传导。NAC的有益作用可能取决于癌症类型是否依赖ROS信号来实现其生存和转移。三阴性乳腺癌（TNBC）具有侵袭性表型，目前主要采用标准化疗作为全身治疗选择。特别是，以 失活和 突变为特征的基底样TNBC细胞会产生高水平的ROS，并依赖ROS信号来实现其生存和恶性进展。此外，TNBC细胞中的高ROS水平可介导癌细胞与组织微环境（TME）之间的相互作用，从而触发基质细胞的募集和转化并诱导缺氧反应，进而导致形成有利于癌症的TME并增加癌症侵袭性。然而，NAC治疗可有效降低ROS的产生以及ROS介导的信号传导，而这些信号传导有助于TNBC细胞的存活、转移和耐药性。因此，在标准化疗中加入NAC可能会为TNBC患者带来额外的益处。
