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Gene & Protein in Disease Cyanine and cancer therapy

predominant modes of cell death (Table 1) [6,8] . Disorders in As bilayer membrane organelles, mitochondria play
apoptotic mechanisms are associated with cancer growth a pivotal role in regulating cell apoptosis and serve as
and confer resistance against tumor therapy . the primary sites for the generation of reactive oxygen
[9]
Apoptosis, recognized as the first identified type of cell species (ROS) [37,38] . Mitochondria undergo dramatic
death, is also known as type I programmed cell death [22,23] . morphological and biochemical changes during apoptosis,
[22,23]
Unlike other forms of cell death, which are not self-inflicted including mitochondrial fission and fusion kinetics .
but rather self-protective and controlled by specific genes, This process involves both division and fusion, with an
apoptosis is a natural and regulated process essential for increase in fission activity and a decrease in fusion activity,
cellular development and death [6,24,25] . Apoptosis plays a thus inducing apoptosis. However, mitochondrial changes
significant role in the elimination of damaged or redundant during apoptosis closely correlate with cancer malignancy
[39]
cells , facilitated by a number of proteins through the and treatment effectiveness . Mitochondria acts as centers
[26]
enzymatic activity of effector cystathionases . Apoptosis for various stressors, and the combination of different
[27]
signal dysregulation and aberrant apoptosis are implicated advent stress signals often precedes the manifestation of
[30]
in the pathogenesis of various diseases, including ectopic apoptotic morphology . ROS can induce intracellular
calcification , neurodegenerative disorders, autoimmune changes in mitochondrial outer membrane permeability
[28]
[6]
diseases, acquired immunodeficiency syndrome (AIDS), (MOMP) by acting on mitochondrial membranes , which
and local ischemia. Thus, apoptosis manifests as a double- are monitored by proteins in the B cell lymphoma 2 (Bcl-2)
edged sword phenomenon for cells . Morphological family, including pro-apoptotic and antiapoptotic proteins,
[29]
[38]
changes in cells are the main characteristics defining whose balance determines cell death and survival .
apoptosis and include cell shrinkage , cell membrane Cytochrome C (Cyto C) is released from mitochondria,
[30]
blebbing, nuclear fragmentation, phosphatidylserine activating the cysteine enzyme cascade reaction, thereby
ectopia, nuclear sequestration, mRNA degradation, inducing apoptosis . Mitochondria amplify the activation
[23]
and apoptotic vesicle formation [6,31-34] . From another of cysteine proteases during apoptosis by releasing Cyto c
perspective, apoptosis is considered an indispensable and other cofactors, accompanied by organelle breakage
[40]
biomarker for certain malignancies. Upregulation of and cristae remodeling . Dysfunctional mitochondria
pro-apoptotic gene expression and downregulation of have implications for many diseases , such as malignant
[41]
antiapoptotic gene expression can better predict the tumors, obesity, glycuresis, and neurodegenerative diseases.
survival time of cancer patients [35,36] . Several studies have demonstrated that the development
Table 1. Classification of cell death patterns
Types of Key proteins Signaling pathways Morphological features Biochemical References
cell death features
Apoptosis Caspase, Bcl-2, BAX, P53, FAS, PTEN/PI3K/AKT, AMPK/AKT, Chromatin condensation, DNA [10,11]
Cytochrome C, BAX MAPK/JNK, AKT/BAD/Bcl-2 karyorrhexis and formation of fragmentation
apoptotic bodies
Necroptosis RIP1, RIP3, MLKL, P38, RIP1/RIP3/MLKL, Plasma membrane rupture, ATP level decrease [12,13]
PGAM5 PKC-MAPK-AP-1 cytoplasmic swelling
Autophagy mTOR, LC3II, Beclin-1, mTOR, Beclin-1, P53, MAPK Formation of double membrane Lysosome activity [14]
DRAM3, TFEB, P62, ULK1 self-solution increased
Ferroptosis GPX4, TFR1, SLC7A11, NRF2, Xc-/GPX4, P53/SLC7A11 Mitochondria decrease or Iron accumulation [15-17]
NCOA4, P53, Ferritin disappear, and the outer
membrane ruptures
Pyroptosis Caspase, NLRP3, GSDMD, NF-κB Infiltration of extracellular The formation [18-21]
IL-1β, IL-18, IL-1α, IL-6, IL-8 contents and cell swelling of inflammatory
vesicles
Abbreviations: AKT: Protein kinase B; AMPK: Adenosine 5’-monophosphate (AMP)-activated protein kinase; ATP: Adenosine triphosphate; BAD: Bcl-xl/
Bcl-2-associated death promoter; BAX: Bcl-2-associated X protein; Bcl-2: B cell lymphoma 2; DRAM-1: Damage-regulated autophagy modulator; FAS:
Apoptosis stimulating fragment; GPX4: Glutathione peroxidase 4; GSDMD: Gasdermin D; IL: Interleukin;
JNK: Recombinant c-Jun N-terminal kinase; LC3II: Light chain 3-II; MAPK: Mitogen-activated protein kinase; MLKL: Mixed lineage kinase domain-like;
mTOR: Mammalian target of rapamycin; NCOA4: Nuclear receptor coactivator 4; NF-κB: Nuclear factor kappa B; NLRP3: NOD-like receptor (NLR)
family pyrin domain-containing 3; Nrf2: Nuclear factor E2-related factor 2; P53: Protein 53; P62: Protein 62; PGAM5: Phosphoglycerate mutase 5;
PI3K: Phosphatidylinositol 3-kinase; PTEN: Phosphatase and tensin homolog deleted on chromosome ten; RIP: Receptor-interacting protein; SLC7A11:
Cystine transporter solute carrier family 7 member 11; TFEB: Transcriptional factor EB; TfR1: Transferrin receptor 1; ULK1: Unc-51 like kinase 1.

Volume 2 Issue 4 (2023) 2 https://doi.org/10.36922/gpd.2486