Proteins Bcl-w , Human
- Known as:
- Proteins Bcl-w , Human
- Catalog number:
- C105
- Product Quantity:
- 10μg
- Category:
- -
- Supplier:
- Novoprotein
- Gene target:
- Proteins Bcl- Human
Related genes to: Proteins Bcl-w , Human
- Gene:
- BCL2 NIH gene
- Name:
- BCL2 apoptosis regulator
- Previous symbol:
- -
- Synonyms:
- Bcl-2, PPP1R50
- Chromosome:
- 18q21.33
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2019-04-23
- Gene:
- BCL2L1 NIH gene
- Name:
- BCL2 like 1
- Previous symbol:
- -
- Synonyms:
- BCLX, BCL2L, Bcl-X, bcl-xL, bcl-xS, PPP1R52
- Chromosome:
- 20q11.21
- Locus Type:
- gene with protein product
- Date approved:
- 1997-10-30
- Date modifiied:
- 2016-01-13
- Gene:
- BCL9L NIH gene
- Name:
- BCL9 like
- Previous symbol:
- -
- Synonyms:
- DLNB11, B9L, Bcl9-2
- Chromosome:
- 11q23.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-12-09
- Date modifiied:
- 2018-11-16
Related products to: Proteins Bcl-w , Human
Related articles to: Proteins Bcl-w , Human
- Breast cancer is a profound cause of mortality among women globally. Similar to BH3 mimetics, targeting the antiapoptotic Bcl-xL:Beclin1 protein complex is crucial to inducing apoptosis and autophagy, thereby suppressing tumor progression in breast cancer cells. This study aims to synthesize and evaluate a series of imidazopyridine-tethered pyrazoline drug prejudice-scaffold derivatives (5a-5l) as Beclin-1 mimetics that induce apoptosis and autophagy and mainly for their potential anticancer activity, focusing on the most potent compound 5c. The primary goal is to assess its ability of compound 5c to inhibit Bcl-xL:Beclin-1 interaction, thereby inducing a protective autophagic response subsequently to assess apoptosis to suppress breast cancer cell proliferation. Molecular docking studies were conducted to evaluate the binding affinity of compound 5c with Bcl-xL, and the interactions were visualized through a three-dimensional interaction map, highlighting key stabilizing interactions. Cytotoxic effects of compound 5c on MCF-7 breast cancer cells were assessed using alamarblue assay. To investigate the antiproliferative potential, colony formation, and wound healing assays were performed at varying concentrations. Apoptotic induction was analyzed through Western blotting for key proteins (BAX, Bcl-xL, Bcl-2), caspase-3/7 activation, and AnnexinV/PI assay using flow cytometry. Additionally, autophagy was examined by monitoring LC3B-I to LC3B-II conversion, Beclin-1 upregulation, and lysosomal activity using LysoTrackerRed staining. The involvement of compound 5c in autophagic flux was further confirmed by quantifying LC3-II accumulation in the presence of an autophagy inhibitor chloroquine (CQ), and then the effect of 5c-induced cell viability and apoptosis were evaluated and caspase-3/7 activity, respectively, during autophagy inhibition condition in MCF-7 cell line. A strong binding interaction of compound 5c with the hydrophobic groove of Bcl-xL demonstrated its potential as an effective Bcl-xL inhibitor. Compound 5c significantly reduced MCF-7 cell viability in a dose-dependent manner (IC50: 9.7 μM). The inhibitory effect of compound 5c on cancer cell proliferation and migration was observed. Treatment with compound 5c induced dose-dependent apoptosis in MCF-7 cells, as confirmed by Annexin V/PI using flow cytometric analysis after 72 h of exposure. A significant decrease in viable cells accompanied by an increase in apoptotic cell populations was observed with increasing concentrations of 5c. Upregulated BAX expression and downregulation in Bcl-xL and Bcl-2 expression levels indicated apoptosis induction. Caspase-3/7 activation further confirmed apoptotic cell death. Autophagy assessment revealed enhanced LC3B-II accumulation, Beclin-1 upregulation, and reduced p62 levels, suggesting modulation of autophagy. CQ treatment further increased LC3-II levels, indicating compound 5c-mediated autophagic flux induction and a significant reduction in cell viability and increased caspase 3/7 activity, confirming modultion of autophagy-dependent apoptosis by 5c. Similar to BH3 mimetic, compound 5c emerges as a promising small-molecule inhibitor targeting the Bcl-xL:Beclin-1 complex, which effectively induces apoptosis by modulating protective autophagy in breast cancer cells. Its dual mechanism of action highlights its potential as a novel therapeutic candidate for breast cancer treatment. - Source: PubMed
Shivakumar RashmiBeeraka Narasimha MOsmani Riyaz Ali MRavi Bhoomika BYadhav Monisha H SNagaraju DileepBhol Chandra SekharNagalakshmi AllakaAhn Kwang SeokNikolenko Vladimir NChinnathambi ArunachalamBender AndreasBasappa Basappa - Adenomyosis is a heterogeneous uterine disorder characterized by the presence of endometrial tissue within the myometrium. Autophagy, a key homeostatic process involved in tissue remodeling and stress adaptation, has been inconsistently described in adenomyosis. This study aimed to define the temporal and compartment-specific regulation of autophagy-associated markers during disease progression, using a tamoxifen-induced CD1 mouse model and human uterine samples. - Source: PubMed
Publication date: 2026/03/25
Vervier JulieSquatrito MarlyneBlacher SilviaNisolle MichelleMunaut Carine - Restoring apoptosis in malignant cells represents a central goal of anticancer therapy. Tumour cells often escape cell death by overexpressing anti-apoptotic members of the BCL-2 protein family, particularly BCL-2, BCL-xL, and MCL1. These proteins inhibit the intrinsic mitochondrial apoptotic pathway through intricate interactions with pro-apoptotic partners and direct modulation of the mitochondrial outer membrane. Their pivotal role in cell survival has established them as attractive therapeutic targets. Over the past two decades, significant efforts have been devoted to developing selective small-molecule inhibitors capable of neutralising these proteins and reactivating apoptosis. A first milestone was the discovery of ABT-263 (navitoclax), a dual BCL-2/BCL-xL inhibitor. Building on this achievement, the development of venetoclax, a highly selective BCL-2 inhibitor, marked a major breakthrough, demonstrating potent pro-apoptotic activity and clinical efficacy in several leukaemia subtypes. Despite these advances, the design of inhibitors of BCL-2 family members remains challenging, largely due to the structural characteristics of the BH3-binding groove, which is both shallow and hydrophobic, complicating the identification of molecules with optimal binding affinity and selectivity. PROTACs targeting BCL-xL may represent a promising future strategy, potentially overcoming the intrinsic limitations of small molecule inhibitors. - Source: PubMed
Cilloni DanielaFerrando AlessandroFrassoni Francesco - T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of T-cell precursors. Although the survival rates have improved with the use of intensive chemotherapy, the emergence of relapse as well as treatment-related morbidity and mortality remain major challenges. Novel treatment approaches include the inhibition of anti-apoptotic regulators or cellular immunotherapies. Here, we analyzed the sensitivity of T-ALL to inhibitors of BCL-2 (venetoclax), BCL-XL (A1331852), MCL-1 (AZD5991) and dual inhibition of BCL-2/BCL-XL (AZD4320) and evaluated their combination effects with natural killer (NK) cells. While only early T-cell precursor (ETP) ALL was sensitive to BCL-2 inhibition, MCL-1 inhibition alone was not effective in most cell lines and patient-derived xenograft (PDX) samples. For BCL-XL and dual BCL-2/BCL-XL inhibition, we observed heterogeneous sensitivities, which were associated with anti-apoptotic dependencies on the respective BCL-2 family members as assessed by BH3-profiling. Moreover, we identified functional shifts in anti-apoptotic dependencies upon exposure to AZD4320 or AZD5991 alone and synergistic effects when both inhibitors were combined with each other, allowing cell death induction in resistant samples. We then explored the potential use of apoptosis-inducing drugs as sensitizers for immunotherapy. Therefore, we investigated the potential of NK cell-mediated killing in T-ALL and found heterogeneous sensitivity, with some cell lines showing responses even at low effector-to-target (E:T) ratios. Importantly, NK cell-mediated killing could be further enhanced by combining NK cells with AZD4320, proposing this combination as a potential effective treatment. Taken together, we demonstrated promising potential of BH3-mimetics and NK cells for the treatment of T-ALL alone and in combination, warranting further preclinical and potential clinical evaluation. - Source: PubMed
Publication date: 2026/04/04
Fortner ColinNiedermayer AlexandraBäuerle Melina MariaWichert Maren ChristianeBraun Christian JörgDebatin Klaus-MichaelVogler MeikeMeyer Lüder HinrichSeyfried Felix - : This research sought to examine the impact of gossypol on cervical cancer tumors that have been transplanted subcutaneously in nude mice, as well as the associated risk of liver damage and its underlying mechanisms. : A subcutaneous cervical cancer tumor model was established in nude mice using the cell suspension inoculation method. Tumor volume and morphological changes in various organs were observed, and the serum concentrations of IL-6, IL-10, and TNF-α were assessed. Protein expression was analyzed using Western blotting. Untargeted metabolomics was employed to identify differential metabolites in mouse liver tissues. Network toxicology was utilized to pinpoint common targets associated with gossypol and hepatotoxicity, followed by KEGG and GO enrichment analyses. Molecular docking was conducted to preliminarily explore the mechanisms underlying gossypol-induced liver injury. : Gossypol significantly suppressed the development of subcutaneous cervical cancer tumors in immunodeficient mice. The Western blotting technique results revealed that increasing doses of gossypol led to a reduction in the expression levels of PIK3R2, GRB2, and MAPK1, compared to the model group ( < 0.05). Untargeted metabolomics revealed 1464 metabolites, from which 9 distinct metabolites were selected for further analysis. Network toxicology results indicated that the hepatotoxicity-related targets of gossypol included MTOR, TNF, CASP3, BCL2L1, and BCL2. KEGG analysis suggested that the toxic mechanisms may be linked to pathways involved in malignancy, the HIF-1 signaling pathway, proteoglycans in cancer, apoptosis, and others. : Gossypol demonstrates a significant therapeutic effect against cervical cancer; however, its hepatotoxicity risk, mediated through multiple targets and pathways, requires further investigation. - Source: PubMed
Publication date: 2026/02/27
Li JinyanParhat ParwenMa YinglanPeng LiuqianLi Min