Interactions of multidomain pro-apoptotic and anti-apoptotic proteins in cancer cell death.

Alexander Chota,Heidi Abrahamse,Blassan P George

doi:10.18632/oncotarget.28031

Alexander Chota, Heidi Abrahamse + Show 1 more

Open Access

https://doi.org/10.18632/oncotarget.28031

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Journal: Oncotarget	Publication Date: Aug 3, 2021
Citations: 30	License type: cc-by

Affiliation: University of Johannesburg

Abstract

Cancer is a global public health concern that is characterized by the uncontrolled growth of tumor cells. It is regarded as the subsequent cause of death after cardiovascular disease. The most common types of cancer include breast, colorectal, lung, and prostate. The risk factors attributed to the development of common types of cancer are tobacco smoking, excessive alcohol consumption, dietary factors, ultraviolet radiation (UV), and lack of physical activities. Two major cellular apoptotic pathways targeted in cancer therapies are intrinsic and extrinsic. These two pathways are regulated by different types of proteins, the multidomain pro-apoptotic proteins (Bak, Bax, and Bok), BH3-only pro-apoptotic proteins (Bid, Bim, Bad, Noxa, and Puma), and the anti-apoptotic proteins (Mcl-1, Bfl-1, Bcl-XL, Bcl-2, Bcl-w, and Bcl-B). Other significant molecules/factors that are known to execute cellular apoptotic pathways include bioactive compounds, and reactive oxygen species (ROS). Proteolytic caspases are known to play a vital role in the initiation of apoptotic activities in cancerous cells. Based on their functions, they are categorized into initiators and executioners. Nanotechnology has produced novel outcomes in modern medicine. The green synthesis of nanoparticles has demonstrated prospective improvements in cancer therapies in combination with the existing therapies including photodynamic therapy. This review aims at highlighting the association between pro-apoptotic and anti-apoptotic proteins, and their significance in cancer therapy.

Highlights

Cancer remains the main public health concern
Bcl-2 family proteins, caspases, and p53 play a significant role in apoptosis
Other than proapoptotic and anti-apoptotic proteins, it is more evident that other mitochondrial components such as cytochrome c contribute to the execution of the mitochondrial www.oncotarget.com outer membrane permeabilization (MOMP) and cellular apoptosis

Summary

Introduction

Cancer remains the main public health concern. Cancer is denoted by the continued growth and proliferation of cancerous cells [1, 2]. There are different types of cancers, the most prevalent types are breast, lung, prostate, and colorectal cancers [4]. In SubSaharan Africa, a high incidence of breast, prostate, and cervical cancers has been reported [5, 6]. Many risk factors attribute to the development of cancer They include tobacco smoking, alcohol consumption, diet, ultraviolet radiation, infections, and lack physical activities [7]. Assessment of these risk factors is a cardinal component of cancer monitoring and evaluation as it gives a comprehensive overview of disease progression [8]. Targeted therapy is one of the promising cancer treatment options that target specific sites such as tumor intracellular organelles and specific proteins involved in tumor development. Oxidative stress on organelles including the mitochondria, and endoplasmic reticulum (ER) is well known to induce the generation of Reactive Oxygen Species (ROS) [9]

Objectives

Conclusion