Bcl-2 Family Members and the Mitochondrial Import Machineries: The Roads to Death

Lalier, Lisenn; Vallette, François M.; Manon, Stéphen

doi:10.3390/biom12020162

Cited by 42 publications

(32 citation statements)

References 135 publications

(167 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These proteins control death signaling through the regulation of the permeabilization of the mitochondrial outer membrane. This is responsible for the release of apoptotic factors, including cytochrome c , which subsequently leads to caspases activation [ 54 , 55 , 56 ]. In human cancers, apoptosis resistance may be due to the downregulation of pro-apoptotic proteins and/or due to the overexpression of anti-apoptotic Bcl-2 family members.…”

Section: Kras Role On Apoptotic Cell Deathmentioning

confidence: 99%

Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications

Ferreira

Pereira

Reis

et al. 2022

Cells

View full text Add to dashboard Cite

KRAS, one of the RAS protein family members, plays an important role in autophagy and apoptosis, through the regulation of several downstream effectors. In cancer cells, KRAS mutations confer the constitutive activation of this oncogene, stimulating cell proliferation, inducing autophagy, suppressing apoptosis, altering cell metabolism, changing cell motility and invasion and modulating the tumor microenvironment. In order to inhibit apoptosis, these oncogenic mutations were reported to upregulate anti-apoptotic proteins, including Bcl-xL and survivin, and to downregulate proteins related to apoptosis induction, including thymine-DNA glycosylase (TDG) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). In addition, KRAS mutations are known to induce autophagy in order to promote cell survival and tumor progression through MAPK and PI3K regulation. Thus, these mutations confer resistance to anti-cancer drug treatment and, consequently, result in poor prognosis. Several therapies have been developed in order to overcome KRAS-induced cell death resistance and the downstream signaling pathways blockade, especially by combining MAPK and PI3K inhibitors, which demonstrated promising results. Understanding the involvement of KRAS mutations in apoptosis and autophagy regulation, might bring new avenues to the discovery of therapeutic approaches for CRCs harboring KRAS mutations.

show abstract

Section: Kras Role On Apoptotic Cell Deathmentioning

confidence: 99%

Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications

Ferreira

Pereira

Reis

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…First, we examined the change in BCL‐2 family proteins, which are critical in the process of apoptosis. Bcl‐2 family members can be divided into proapoptotic group and antiapoptotic group according to their role in the process of apoptosis (Lalier et al, 2022). The proapoptotic Bcl‐2 members such as Bax and Bak are able to form and/or active pores in mitochondria (Lalier et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

OSU‐T315 and doxorubicin synergistically induce apoptosis via mitochondrial pathway in bladder cancer cells

Ren

Chen

et al. 2022

Cell Biology International

View full text Add to dashboard Cite

Bladder cancer (BC) is a common urological malignancy that still lacks an effective treatment. Doxorubicin (Dox) has been widely used in the treatment of various cancers, including BC. However, chemoresistance often hampers the clinical application of Dox, therefore, it is necessary to develop effective strategies to improve its efficacy. By using high-throughput screening, we identified OSU-T315, an integrin-linked kinase (ILK) inhibitor, that can augment the cytotoxicity of Dox against BC cells. We found that OSU-T315 and Dox synergistically induce apoptosis of BC cells via mitochondrial pathway in a caspase-dependent. Mechanically, it was found that OSU-T315 and Dox synergistically induced activation of Bax which is critical for the induction of apoptosis. Moreover, it was also found that the downregulation of BCL-2 and MCL-1 is essential for the activation of BAX induced by OSU-T315 and Dox.OSU-T315 was found to downregulate MCL-1 via the GSK-3β/FBXW7 axis in BC cells. Our findings suggest that combined treatment with OSU-T315 and Dox may be a promising strategy to treat BC.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The important role of BCL-2 family members in regulating apoptosis has been elucidated in the literature [ 33 ]. It is well known that an anti-apoptotic member of the BCL-2 family (such as BCL2 protein) is down-regulated in mitochondria-mediated apoptosis while the proapoptotic members of the BCL-2 family (such as BAX and BAD), in addition to apoptotic signaling molecules (such as cleaved PARP), are upregulated in apoptosis [ 33 ]. Our findings are consistent with this mechanism where STZ treatment induces apoptosis apparently through mitochondria-mediated pathways through downregulating BCL2 expression, while BAX and BAD were upregulated.…”

Section: Discussionmentioning

confidence: 99%

Carnosic Acid Protects INS-1 β-Cells against Streptozotocin-Induced Damage by Inhibiting Apoptosis and Improving Insulin Secretion and Glucose Uptake

et al. 2022

View full text Add to dashboard Cite

Carnosic acid (CA), a natural polyphenolic diterpene derived from Rosmarinus officinalis, has been proven to possess a broad spectrum of medicinal properties. Nevertheless, no studies on its impact on pancreatic β-cells have been conducted to date. Herein, clonal rat INS-1 (832/13) cells were pretreated with CA for 24 h and then incubated with streptozotocin (STZ) for 3 h. Several functional experiments were performed to determine the effect of CA on STZ-induced pancreatic β-cell damage, including cell viability assay, apoptosis analysis, and measurement of the level of insulin secretion, glucose uptake, malondialdehyde (MDA), reactive oxygen species (ROS), and proteins expression. STZ treatment decreased cell survival, insulin secretion, glucose uptake, and increased apoptosis, MDA, and ROS production in INS-1 cells. Furthermore, protein expression/phosphorylation analysis showed significant down-regulation in insulin, PDX-1, PI3K, AKT/p-AKT, and Bcl2. On the other hand, expression of BAX and BAD and cleaved PARP were significantly increased. Interestingly, preincubation with CA reversed the adverse impact of STZ at the cellular and protein expression levels. In conclusion, the data indicate that CA protects β-cells against STZ-induced damage, presumably through its modulatory effect on the different pathways, including the Pi3K/AKT/PDX-1/insulin pathway and mitochondria-mediated apoptosis.

show abstract

Bcl-2 Family Members and the Mitochondrial Import Machineries: The Roads to Death

Cited by 42 publications

References 135 publications

Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications

Crucial Role of Oncogenic KRAS Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications

OSU‐T315 and doxorubicin synergistically induce apoptosis via mitochondrial pathway in bladder cancer cells

Carnosic Acid Protects INS-1 β-Cells against Streptozotocin-Induced Damage by Inhibiting Apoptosis and Improving Insulin Secretion and Glucose Uptake

Contact Info

Product

Resources

About