The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

Qian, Shanna; Wang, Zhong; Yang, Wanting; Huang, Jinling; Yang, Yinfeng; Wang, Jinghui

doi:10.3389/fonc.2022.985363

Cited by 247 publications

(147 citation statements)

References 162 publications

(174 reference statements)

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“…Apoptosis is a common form of cell death; hence we first explored the expressions of apoptotic proteins in A549/CDDP cells. The Bcl‐2 protein family functions as promoters or inhibitors of cell death, [47] and the p53 protein is critical to DNA damage, apoptosis and drug resistance [48] . The effect of FP and DFP on these proteins were determined by western blotting.…”

Section: Resultsmentioning

confidence: 99%

Overcoming Cancer Resistance to Platinum Drugs by Inhibiting Cholesterol Metabolism

Wang,

Cai,

et al. 2023

Angew Chem Int Ed

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Drug resistance is a serious challenge for platinum anticancer drugs. Platinum complexes may get over the drug resistance via a distinct mechanism of action. Cholesterol is a key factor contributing to the drug resistance. Inhibiting cellular cholesterol synthesis and uptake provides an alternative strategy for cancer treatment. Platinum(IV) complexes FP and DFP with fenofibric acid as axial ligand(s) were designed to combat the drug resistance through regulating cholesterol metabolism besides damaging DNA. In addition to producing reactive oxygen species and active platinum(II) species to damage DNA, FP and DFP inhibited cellular cholesterol accumulation, promoted cholesterol efflux, upregulated peroxisome proliferator‐activated receptor alpha (PPARα), induced caspase‐1 activation and gasdermin D (GSDMD) cleavage, thus leading to both apoptosis and pyroptosis in cancer cells. The reduction of cholesterol significantly relieved the drug resistance of cancer cells. The double‐acting mechanism gave the complexes strong anticancer activity in vitro and vivo, particularly against cisplatin‐resistant cancer cells.

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Section: Resultsmentioning

confidence: 99%

Overcoming Cancer Resistance to Platinum Drugs by Inhibiting Cholesterol Metabolism

Wang,

Cai,

et al. 2023

Angew Chem Int Ed

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“…On the other hand, BCL2 proteins are anti-apoptotic factors. Targeting these proteins by developing new drugs could help regulate apoptosis and thus anti-cancer therapy [40]. Increasing evidence has shown that the downregulation of CASP3 is correlated with the development of BC [39].…”

Section: Discussionmentioning

confidence: 99%

Expression of microRNAs ‘let-7d and miR-195’ and apoptotic genes ‘BCL2 and caspase-3’ as potential biomarkers of female breast carcinogenesis

Ibrahim,

Hegazy,

Gobran

et al. 2023

Preprint

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Background Breast cancer (BC) is the most common cause of cancer-related death among women world-wide. Let-7d and microRNA-195 (miR-195) are members of microRNAsthat are well-known tumor suppressors involved in the regulation of apoptosis, invasion, and other cellular functions. However, the roles of these microRNAs in BC progression remain controversial. This study aimed to explore the correlation between the expression of let-7d and miR-195 and apoptosis-related genes (ARG) “B-cell lymphoma 2 (BCL2) and caspase-3 (CASP3)” as potential biomarkers of breast carcinogenesis. Methods It was a retrospective case-control study where expression of let-7d, miR-195, CASP3, and BCL2 was evaluated using quantitative real-time PCR (qRT-PCR); and immunohistochemical (IHC) staining was used to determine expression of BCL2 and CASP3 in BC tissues versus normal breast tissues (NT)samples. Results Expression of let-7d and miR-195 was significantly reduced within BC tissues compared to NT (P: < 0.0001); and there was a statically positive correlation between them (r=0.314, P: 0.005). They have also been correlated to biomarkers’ expression of genes related to apoptosis. There was a statistically significant positive association between CASP3, and both let-7d, and miR-195 relative gene expression (r=0.713, P: <0.0001 and r=0.236, P: 0.03, respectively); in contrast, there was a statistically significant negative association between the relative gene expression of BCL2, and let-7d, and miR-195 (r=-0.221, P: 0.04 and r=-0.311, P: 0.005, respectively). Conclusions Let-7d and miR-195 have been suggested to be involved in BC by modulating the ARG including BCL2 and CASP3. The qRT-PCR and IHC studies verified that low expression of let-7d and miR-195 prohibit apoptosis via downregulating CASP3 and increasing BCL2 expressions promoting BC progression These results also hypothesize that let-7d and miR-195 along with apoptotic biomarkers (BCL2 and CASP3) can be used in the future to introduce novel, non-invasive molecular biomarkers for BC into clinical practice.

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“…Apoptosis is initiated by proapoptotic proteins with one BH domain, such as borane. The Bcl‐2 protein family, encoded by the BIM gene, is one of the most active proapoptotic proteins 80 . The proapoptotic proteins Bcl‐2‐related X protein (BAX) and Bcl‐2 antagonist/killer (BAK) help activate proapoptotic proteins or promote protein pore formation.…”

Section: Mitochondrial Pathway Of Apoptosismentioning

confidence: 99%

ZnO nanomaterials target mitochondrial apoptosis and mitochondrial autophagy pathways in cancer cells

Li,

et al. 2024

Cell Biochemistry & Function

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In recent years, the application of engineering nanomaterials has significantly contributed to the development of various biomedical fields. Zinc oxide nanomaterials (ZnO NMts) have gained wide popularity due to their biocompatibility, unique physical and chemical properties, stability, and cost‐effectiveness for large‐scale production. They have emerged as potential materials for anticancer applications. This article provides a comprehensive review of the synthesis methods of ZnO NMts and highlights the advantages of combining ZnO NMts with anticancer drugs as a nano platform for cancer treatment. Additionally, the article briefly explains the mechanism of action of ZnO NMts in tumor cells, focusing on the mitochondrial pathways that target cell apoptosis and autophagy. It is observed that these pathways are primarily influenced by reactive oxygen species generated through oxidative stress. The article discusses the promising prospects of ZnO NMts combined with anticancer drugs in the field of cancer medicine and emphasizes the need for further in‐depth research on the mitochondrial apoptosis and mitochondrial autophagy pathways.

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The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

Cited by 247 publications

References 162 publications

Overcoming Cancer Resistance to Platinum Drugs by Inhibiting Cholesterol Metabolism

Overcoming Cancer Resistance to Platinum Drugs by Inhibiting Cholesterol Metabolism

Expression of microRNAs ‘let-7d and miR-195’ and apoptotic genes ‘BCL2 and caspase-3’ as potential biomarkers of female breast carcinogenesis

ZnO nanomaterials target mitochondrial apoptosis and mitochondrial autophagy pathways in cancer cells

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