Abstract
The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic apoptosis to terminate damaged cells. Insight into these mechanisms and the associated physicochemical properties and biomolecular interactions of Cyt c informs on the anticancer therapeutic potential of the protein, especially in its ability to subvert the current limitations of small molecule-based chemotherapy. In this review, we explore the development of Cyt c as an anticancer drug by identifying cancer types that would be receptive to the cytotoxicity of the protein and factors that can be finetuned to enhance its apoptotic potency. To this end, some information is obtained by characterizing known drugs that operate, in part, by triggering Cyt c induced apoptosis. The application of different smart drug delivery systems is surveyed to highlight important features for maintaining Cyt c stability and activity and improving its specificity for cancer cells and high drug payload release while recognizing the continuing limitations. This work serves to elucidate on the optimization of the strategies to translate Cyt c to the clinical market.
Highlights
cytochrome c (Cyt c) is a ubiquitous protein that plays a key role in the electron transport chain (ETC), in serving as a redox agent, in regulating reactive oxygen species (ROS), and in inducing apoptosis in eukaryotes (Figure 2)
This substitution is observed for Cyt c molecules that interact with cardiolipin (CL, a phospholipid of the mitochondrial membrane)
Due to their high reactivity, they may become harmful to the cell in large quantities, as they are capable of oxidizing species, such as lipids, proteins, and DNA (Figure 8C)
Summary
To circumvent the limitations of standard chemotherapeutics, targeted therapeutic drugs are emerging as prime cancer treatments In this treatment space, the use of small molecules, namely protein inhibitors, remains quite pertinent [9]. This review serves to provide an overview of the efforts of numerous research teams to develop Cyt c as an anticancer drug by establishing a proficient drug delivery system and formulation to overcome the cell impenetrability of the protein and to enable specificity for cancer cells. By learning from these efforts and highlighting important structural details of the protein essential for activity, the ultimate objective is to shed light on an optimal approach to translate Cyt c to the drug market
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