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Gene & Protein in Disease Cyanine and cancer therapy

P53 promotes apoptosis by upregulating the and autophagy [166] . It regulates glucose and lipid metabolism
transcription of pro-apoptotic proteins, including death through its interaction with ATP [167] , adenosine diphosphate
receptor 5 (DR5), FAS, and TNF-receptor type I (TNF- (ADP), and adenosine monophosphate (AMP), thereby
R1), leading to the activation of caspase-8 [143,144] . Moreover, modulating the mitochondrial energy of cells [168,169] .

P53 induces the activation of PUMA, BAX, BID, Bcl-xl/ The disruption of oxidative phosphorylation results in
Bcl-2-associated death promoter (BAD), BAK, and NOXA a decrease in mitochondrial energy content, leading to
(PMAIP1) [82,145-147] . One mechanism by which P53 enhances an increase in the ADP/ATP or AMP/ATP ratio and
cysteine protease activation is to induce BID, BAK, and BAX subsequent activation of AMPK [154] . Surprisingly, AMPK
to increase MOMP [49,148] . The presence of P53 is significantly may exert either pro- or anti-tumor effects depending on the
correlated with increased transcriptional activation of ARTS, metabolic environment [170] . Under conditions of metabolic
a pro-apoptotic XIAP antagonist that counteracts XIAP stress, AMPK may promote tumorigenesis by stimulating
inhibition of cysteine proteases, resulting in BID activation alternative metabolic pathways such as mitochondrial
and mitochondrial outer membrane permeabilization [121,122] . phagocytosis and fatty acid combustion, thereby promoting
Moreover, P53 plays a key role in germ cell apoptosis metabolic plasticity. In addition, AMPK interacts with
across various animals, including mammals and reptiles. AKT, a key regulator of nutrient availability. Activation by
Its mechanism involves the regulation of apoptosis-related AKT promotes glycolysis by upregulating hexokinase-2,
proteins such as BID, BAX, Bcl-xl, and Bcl-2, as well as death which in turn affects mitochondrial permeability and
receptors such as CD95, FAS, Apo-1, and DR5 [149] . apoptosis [171] . Furthermore, AKT can activate mTORC1/2,
subsequently modulating downstream apoptosis signaling
4. Signaling pathways of apoptosis pathways [172-174] .
4.1. PTEN/PI3K/AKT
4.3. MAPK/JNK
PTEN/PI3K/AKT plays a key role in apoptosis and is often
activated in cancer [150,151] . Phosphatase and tensin homolog The mitogen-activated protein kinase (MAPK) pathway
deleted on chromosome ten (PTEN) is a dual protein transmits extracellular signals to regulate apoptosis. Recent
that primarily dephosphorylates phosphatidylinositol studies have presented different opinions on the role of
(3,4,5)-trisphosphate, and its activity is lost in human the MAPK/JNK pathway in controlling apoptosis under
cancers [152] . PI3K, a lipid kinase, regulates various cellular genotoxic stress. Further understanding of the effect of
processes and is implicated in chemotherapy resistance MAPK/JNK on apoptosis regulation holds promise for early
in cancer therapy . AKT, a threonine/serine protein cancer treatment prognosis [175] . Phosphorylated (p)-JNK
[75]
kinase, serves as a vital downstream effector in the PI3K/ localizes to mitochondria, resulting in mitochondrial
AKT signaling pathway. It exists in three forms: AKT1 dysfunction characterized by decreased energy supply,
(predominantly expressed in most tissues), AKT2 (mainly disrupted MOMP, increased ROS production, and ultimately
found in insulin-sensitive tissues such as the liver, pancreas, leading to apoptosis. This process involves the translocation
and muscle), and AKT3 (expressed in the cerebrum and of BAX to the outer mitochondrial membrane, leading to the
orchis). Phosphorylation of Thr308 and Ser473 activates widening of the pores in the outside membrane and apoptosis
AKT, which in turn mediates apoptosis and cell cycle [153-158] . induction [162] . JNK, a member of the MAPK family, also
Numerous studies have illustrated a significant correlation known as stress-activated kinases, comprises three coding
between increased expression of Bcl-2 and aberrant activation genes: JNK1, JNK2, and JNK3 [176,177] . While JNK1 and JNK2
of the PTEN/PI3K/AKT signaling pathway [159-162] . However, are generally expressed in various tissues, JNK3 is mainly
further investigation of this signaling pathway is essential for expressed in the brain and heart [177,178] . Specific stimuli, such as
gaining insights and developing strategies for cancer therapy. MKK4 and MKK7, activate JNK through phosphorylation [179]
and regulate the phosphorylation and activity of downstream
4.2. AMPK/AKT factors [180-182] . In summary, MAPK/JNK plays a significant
Adenosine 5‘-monophosphate(AMP)-activated protein role in mitochondria-induced apoptosis [183] .
kinase (AMPK) is an energetic cell sensor and plays an 5. Apoptosis induction based on cyanine
essential role in the apoptosis signaling pathway [163] . It exists
as a heterotrimer complex comprised of α, β, and γ subunits, Cyanine was first discovered by Williams in 1856. It
where β and γ serve as regulatory subunits while α serves possesses fluorescence emission characteristics and
as a catalytic subunit. Phosphorylation of threonine residue serves as a fluorescent dye [184] . The chemical structure of
172 on the α subunit is a significant process in activating cyanine consists of two components: a conjugated chain of
AMPK [164,165] . AMPK is involved in various biological multiple methylene groups and a cyclic structure, such as
regulatory processes, including apoptosis, proliferation, an aromatic, heterocyclic, or cyclic alkene, attached at the

Volume 2 Issue 4 (2023) 7 https://doi.org/10.36922/gpd.2486