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Gene & Protein in Disease Cyanine and cancer therapy

Table 2. Classification of apoptotic proteins
Classification of Specific Specific proteins Function References
apoptotic proteins families
Pro-apoptotic proteins Caspase family Caspase-2, -8, -10 Apoptosis activator caspases [74]
Caspase-3, -6, -7 Downstream apoptosis executioner caspase [74]
Caspase-1, -4, -5 Downstream substrates of inflammatory mediator caspases [74]
Apaf-1 A critical molecule in the intrinsic or the mitochondrial [85]
signal way of apoptosis
Bcl-2 family Bcl-xs, BAK 2, BAK 3, [86]
BAD, BID, BIK, HRK
FAS Caspase activator [87]
P53 Monitor and induce apoptosis of abnormal cells [88]
Myc Promote cell proliferation or apoptosis [89]
ATM DNA damage test [90]
Anti-apoptotic proteins Bcl-2 family Bcl-2, Bcl-xl, Bcl-w, MCL-1, A 1, Bfl-1 [86]
Abbreviations: Apaf-1: Apoptotic protease activating factor 1; ATM: Ataxia telangiectasia mutated kinase; BAD: Bcl-xl/Bcl-2-associated death
promoter; BAK: Bcl-2 antagonist/killer 1; Bcl: B cell lymphoma; BID: Bcl-2 homology 3 interacting domain death agonist; BIK: BCL-2 interacting
killer; FAS: Apoptosis stimulating fragment; MCL-1: Myeloid cell leukemia-1.

caspase-3 is the predominant lytic enzyme that promotes ubiquitinate Bcl-2 and degrade it by the proteasome [132] ,
apoptosis [108,109] . Previous studies have detected caspase-3 in thereby highlighting the significant role of Bcl-2 in apoptosis.
a considerable number of human cancers, including non-
small cell lung cancer [110] , esophageal squamous carcinoma, 3.3.2. Protein 53
and gastric cancer [111,112] . Recent studies have demonstrated The oncogene protein 53 (P53) plays a significant role in
that RNA interference (RNAi) technology can rapidly and cancer by orchestrating diverse cellular processes such as cell
specifically silence caspase-3 gene expression, offering a new cycle arrest, apoptosis, DNA repair, senescence metabolism,
option for antiapoptotic therapy [113] . and antioxidant response [121,133,134] . Notably, the activation of
P53 primarily leads to cell cycle arrest and apoptosis [121] . P53
3.3. Antiapoptotic proteins is among the most frequently mutated or silenced genes in
3.3.1. BCL-2 malignant tumors and has been extensively investigated in
recent years. Its activation serves as a protective mechanism
Bcl-2, functioning as a proto-oncogene, serves as a pivotal against tumorigenesis and promotes the efficacy of tumor
regulator for cell death, inhibiting apoptosis and being eradication therapies. In response to cellular stress,
closely related to the pathogenesis and resistance to various P53 modulates both intrinsic and extrinsic apoptosis
anticancer drugs [114-117] . Previous research has demonstrated pathways [135] . Furthermore, P53 can directly influence
that elevated levels of Bcl-2 in malignant cells can confer mitochondria, participating in and inducing apoptosis [136] .
resistance to apoptosis induced by chemotherapy drugs such Mechanistically, interactions between P53 and members
as cisplatin and arsenic trioxide [118-120] . Conversely, inhibition of the Bcl-xl and pro-apoptotic Bcl-2 family liberate the
of Bcl-2 expression can trigger apoptosis in tumor cells. pro-apoptotic effector BAX/BAK, thereby triggering the
Overexpression of Bcl-2 has been associated with apoptosis release of Cyto C and activating pro-caspase-3 [137] . P53-
resistance in a considerable number of human malignant induced apoptosis involves the regulation of apoptosis-
tumors, including B-cell lymphoma, prostate carcinoma, and associated proteins whose expression is controlled by P53.
melanoma [49,121-124] . In addition, previous studies have revealed Furthermore, P53 induces apoptosis by initiating the release
overexpression of Bcl-xl in CRC and Kaposi’s sarcoma [125,126] . of Cyto C from mitochondria through mitochondrial
Therefore, the overexpression of Bcl-2 and Bcl-xl has been translocation [138-140] . Mutations in the p53 gene are present
implicated in cisplatin resistance and malignant tumor in more than half of all human malignancies. Introducing
recurrence rates across various cancers, including non-small functional P53 into tumor cells containing mutant P53 can
cell lung, head-and-neck cancer, and breast cancers [127-131] . induce apoptosis and suppress tumor growth. Consequently,
On the initiation of apoptosis, the scaffolding protein ARTS P53 is considered the most critical mediator of tumor cell
facilitates the formation of a ternary complex involving apoptosis and is a key target in various anti-cancer therapies,
Bcl-2, ARTS, and XIAP. This complex allows XIAP to including chemotherapy and radiation therapy [141,142] .

Volume 2 Issue 4 (2023) 6 https://doi.org/10.36922/gpd.2486