Cytochrome c in cancer therapy and prognosis

Abstract

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.

Secretome analysis of breast cancer cells to identify potential target proteins of Ipomoea turpethum extract-loaded nanoparticles in the tumor microenvironment

“…Complement C3 known for facilitating metastasis is downregulated in the counterpart TNBC MDA MB-231 cell line, suggesting that NVA-IT uniquely targets the same protein in different subtypes. Similarly, cytochrome C (CYCS), a well-known apoptosis player, is highly upregulated in MCF-7 (fold change 5) but downregulated in MDA MB-231 (Jiang and Wang, 2004a;Pessoa, 2022). MCF-7 and MDA MB-231 represent the two different phenotypes of breast cancer based on the expression of estrogen receptors, i.e., ER+ and ER−, respectively (Alghanem et al, 2020).…”

The Role of Oxidative Stress in Tumorigenesis and Progression

“…The first is the mitochondrial apoptotic pathway. Oxidative stress stimulation directly affects mitochondrial membrane potential by disrupting mitochondrial inner membrane permeability [ 127 ], mediating pathways like bax/bcl-2-cyt-c [ 128 ] and p38 MAPK, and phosphorylating HSP27 [ 129 ], all of which promotes the release of cytochrome c (Cyt c) and activates caspase families, directly driving cancer cell apoptosis [ 130 ]. Notably, the mitochondrial permeability transition pore (MPTP) integrates ROS-induced cell apoptosis and calcium signaling through activation by both ROS and Ca 2+ , ensuing an influx of Ca 2+ and release of Cyt c [ 131 ].…”

“…Mitochondria play a key role in apoptosis and ferroptosis of tumor cells. Mitochondria are the executors of the intrinsic pathway of apoptosis, with apoptosis-related proteins such as the Bcl-2 family proteins and Cyt C[130]. Besides controlling ROS levels, mitochondria also contain large amounts of irons and possess the ability to take up iron.…”

Intracellular Protein Delivery: Approaches, Challenges, and Clinical Applications

“…Similarly, proteins inhibiting essential cellular functions offer a direct method to kill cancer cells and suppress tumor growth. Proteases [ 43 , 44 ], bacterial toxins [ 45 ], and apoptosis inducers [ 46 ] are promising candidates for cancer therapeutics. Saporin is a highly active inhibitor of protein synthesis and of high interest for potent suppression of tumor cells [ 47 ].…”