CNC - Center for Neuroscience and Cell Biology, CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal.
Biosci Rep. 2022 Dec 22;42(12). doi: 10.1042/BSR20222171.
Cytochrome c (cyt c) is an electron transporter of the mitochondrial respiratory chain. Upon permeabilization of the mitochondrial outer membrane, cyt c is released into the cytoplasm, where it triggers the intrinsic pathway of apoptosis. Cytoplasmic cyt c can further reach the bloodstream. Apoptosis inhibition is one of the hallmarks of cancer and its induction in tumors is a widely used therapeutic approach. Apoptosis inhibition and induction correlate with decreased and increased serum levels of cyt c, respectively. The quantification of cyt c in the serum is useful in the monitoring of patient response to chemotherapy, with potential prognosis value. Several highly sensitive biosensors have been developed for the quantification of cyt c levels in human serum. Moreover, the delivery of exogenous cyt c to the cytoplasm of cancer cells is an effective approach for inducing their apoptosis. Similarly, several protein-based and nanoparticle-based systems have been developed for the therapeutic delivery of cyt c to cancer cells. As such, cyt c is a human protein with promising value in cancer prognosis and therapy. In addition, its thermal stability can be extended through PEGylation and ionic liquid storage. These processes could contribute to enhancing its therapeutic exploitation in clinical facilities with limited refrigeration conditions. Here, I discuss these research lines and how their timely conjunction can advance cancer therapy and prognosis.
细胞色素 c(cyt c)是线粒体呼吸链的电子转运体。在线粒体外膜通透化后,cyt c 被释放到细胞质中,在细胞质中触发细胞凋亡的内在途径。细胞质中的 cyt c 可以进一步进入血液。凋亡抑制是癌症的标志之一,其在肿瘤中的诱导是一种广泛应用的治疗方法。凋亡抑制与诱导分别与 cyt c 血清水平的降低和升高相关。血清中 cyt c 的定量在监测患者对化疗的反应方面很有用,具有潜在的预后价值。已经开发了几种高灵敏度的生物传感器来定量人血清中的 cyt c 水平。此外,将外源性 cyt c 递送至癌细胞的细胞质是诱导其凋亡的有效方法。同样,已经开发了几种基于蛋白质和基于纳米颗粒的系统来将 cyt c 递送至癌细胞用于治疗。因此,cyt c 是一种具有潜在价值的人类蛋白,可用于癌症的预后和治疗。此外,通过聚乙二醇化和离子液体储存可以延长其热稳定性。这些过程可能有助于在冷藏条件有限的临床设施中增强其治疗性利用。在这里,我讨论了这些研究方向,以及它们的及时结合如何能促进癌症的治疗和预后。