Independent Researcher, Bhopal, Madhya Pradesh, 462020, India.
Department of Pathology & Lab Medicine, All India Institute of Medical Sciences-Bhopal, Saket Nagar, Bhopal, Madhya Pradesh, 462020, India.
Curr Mol Med. 2024;24(2):205-216. doi: 10.2174/1566524023666230309112751.
Redox homeostasis is essential for keeping our bodies healthy, but it also helps breast cancer cells grow, stay alive, and resist treatment. Changes in the redox balance and problems with redox signaling can make breast cancer cells grow and spread and make them resistant to chemotherapy and radiation therapy. Reactive oxygen species/reactive nitrogen species (ROS/RNS) generation and the oxidant defense system are out of equilibrium, which causes oxidative stress. Many studies have shown that oxidative stress can affect the start and spread of cancer by interfering with redox (reduction-oxidation) signaling and damaging molecules. The oxidation of invariant cysteine residues in FNIP1 is reversed by reductive stress, which is brought on by protracted antioxidant signaling or mitochondrial inactivity. This permits CUL2FEM1B to recognize its intended target. After the proteasome breaks down FNIP1, mitochondrial function is restored to keep redox balance and cell integrity. Reductive stress is caused by unchecked amplification of antioxidant signaling, and changes in metabolic pathways are a big part of breast tumors' growth. Also, redox reactions make pathways like PI3K, PKC, and protein kinases of the MAPK cascade work better. Kinases and phosphatases control the phosphorylation status of transcription factors like APE1/Ref-1, HIF-1, AP-1, Nrf2, NF-B, p53, FOXO, STAT, and - catenin. Also, how well anti-breast cancer drugs, especially those that cause cytotoxicity by making ROS, treat patients depends on how well the elements that support a cell's redox environment work together. Even though chemotherapy aims to kill cancer cells, which it does by making ROS, this can lead to drug resistance in the long run. The development of novel therapeutic approaches for treating breast cancer will be facilitated by a better understanding of the reductive stress and metabolic pathways in tumor microenvironments.
氧化还原平衡对于保持身体健康至关重要，但它也有助于乳腺癌细胞生长、存活和抵抗治疗。氧化还原平衡的变化和氧化还原信号的问题会使乳腺癌细胞生长和扩散，并使它们对化疗和放疗产生耐药性。活性氧/活性氮（ROS/RNS）的产生和氧化剂防御系统失去平衡，导致氧化应激。许多研究表明，氧化应激可以通过干扰氧化还原（还原-氧化）信号和损伤分子来影响癌症的发生和扩散。FNIP1 中不变半胱氨酸残基的氧化可以被还原性应激逆转，还原性应激是由持续的抗氧化信号或线粒体失活引起的。这使得 CUL2FEM1B 能够识别其预期的靶标。FNIP1 被蛋白酶体降解后，线粒体功能得到恢复，以保持氧化还原平衡和细胞完整性。还原性应激是由抗氧化信号的失控放大引起的，代谢途径的变化是乳腺癌生长的一个重要部分。此外，氧化还原反应使 PI3K、PKC 和 MAPK 级联中的蛋白激酶等途径更好地发挥作用。激酶和磷酸酶控制转录因子如 APE1/Ref-1、HIF-1、AP-1、Nrf2、NF-B、p53、FOXO、STAT 和 -连环蛋白的磷酸化状态。此外，支持细胞氧化还原环境的元素协同作用的好坏，也会影响抗乳腺癌药物，特别是那些通过产生 ROS 来引起细胞毒性的药物的治疗效果。虽然化疗旨在通过产生 ROS 来杀死癌细胞，但从长远来看，这可能会导致耐药性。更好地了解肿瘤微环境中的还原性应激和代谢途径将有助于开发治疗乳腺癌的新治疗方法。
