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

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-X L , 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 antiapoptotic proteins, and their significance in cancer therapy.

Tetramethylpyrazine: An Active Ingredient of Chinese Herbal Medicine With Therapeutic Potential in Acute Kidney Injury and Renal Fibrosis

“…Unlike necrosis, apoptosis does not cause inflammation ( Kønig et al, 2019 ). When a cell receives an apoptosis signal, it activates the initial caspases through different signaling pathways, reactivates the effector caspases, and degrades related substrates, eventually leading to cell apoptosis ( Chota et al, 2021 ). Since there are many apoptotic signaling pathways, the upstream regulation of caspases is also different.…”

Combination Treatment of Sorafenib and Bufalin Induces Apoptosis in NCI-H292 Human Lung Cancer CellsIn Vitro

“…Our results revealed that the two-drug combination shows the lower expression of Bcl-2 (anti-apoptotic protein) and higher levels of Bax and Bad (pro-apoptotic proteins) in NCI-H292 cells as compared to sorafenib or bufalin treatment alone (Figure 5B). Once activated, both Bak and Bax oligomerize on the outer mitochondrial membrane to drive its rupture and then result in the initiation of the intrinsic apoptosis pathway in the mitochondrial compartment (45). Furthermore, the combination treatment also resulted in higher cytochrome c and APAF-1 levels in addition to the active form of caspase-3 and -9 than that upon treatment with sorafenib or bufalin alone (Figure 5C and D).…”

Nutraceuticals and Cancer: Potential for Natural Polyphenols

“…Citrus fruits represent major sources of flavonoids. Several experimental studies have strongly indicated that bergamot and its extracts can exert antitumor effects thanks to the ability of flavonoids to interfere with the main stages of carcinogenicity: the onset, promotion, and progression of cancer [116]. The anticancerous action of BEO has been adequately highlighted in several in vitro works.…”

“…In particular, a reduction in cell proliferation was triggered by the shutdown of the cell cycle in phase G0-G1. In addition, intense pro-oxidant activity and cellular DNA damage have been appreciated [80,116,117]. A very comprehensive work [118] conducted in vitro on human cancerous cells of the nervous system (SH-SY5Y, PC12), prostate (PC3), and breast (MDA-MB-231) showed that treatment with BJ at different concentrations (1-5%) arrested cancer progression.…”

“…There are several studies describing how oleuropein, in addition to reducing ROS, decreased the expression of histone deacetylase, induced apoptotic death, and delayed the migration and invasion of cells in a dose-dependent manner. In addition, oleuropein induced the downregulation of metalloproteinase genes, which may be involved in the prevention of breast cancer metastases [113,116,181]. An antioxidant and growth inhibitory effect was found for differentiated thyroid cancer [115].…”