BCL2L1 (BCL2-like 1)

These results suggest that E-BVL may influence apoptotic and proliferative pathways in THP-1 leukemia cells. Overall, this study highlights B. vulgaris leaf extract as a promising natural source of bioactive compounds for anti-leukemic research, without specifically implicating berberine, which was not detected in the extract.

Clinically, the BCL-2 inhibitor venetoclax has revolutionized CLL and acute myeloid leukemia (AML) treatment, showing efficacy in TP53-mutant CLL and elderly AML patients when combined with CD20 antibodies or hypomethylating agents...This review highlights the clinical success of BCL-2 inhibitors, addresses resistance mechanisms, and explores future directions, including sublethal MOMP, inflammatory outcomes, and novel inhibitors. Celebrating the collaborative, interdisciplinary efforts that transformed fundamental discoveries into life-saving therapies, this account underscores both the triumphs and the "potholes" encountered on the path to understanding apoptosis, while identifying open questions for ongoing research.

Inflachromene, an inhibitor of the chromatin remodelers HMGB1/2, decoupled mitochondrial bioenergetics from senolytic susceptibility, yielding SASP-null/miR146a-negative senescent cancer cells that were completely resistant to ABT-263/navitoclax and A1331852 despite extensive mitochondrial reprogramming. Thus, the senolytic response is governed by a layered circuit in which mitochondrial bioenergetic heritage establishes the senolytic ceiling, TIS-acquired bioenergetic flexibility fine-tunes the amplitude of the senolytic response, and establishing a mitochondria-inflammatory SASP crosstalk is required for BH3-mediated senolysis. These results support using functional readouts that integrate mitochondrial metabolic flexibility and inflammatory SASP to predict and potentially enhance senolytic efficacy in TIS cancer cells.

Collectively, IMB5023 concurrently disrupts microtubules and inhibits STAT3 pathway. This dual mechanisms of action positions IMB5023 as a promising therapeutic candidate, particularly for resistant malignancies.

Gene expression analysis showed upregulation of FAS (1.67-fold; P<0.001), FASL (1.28 fold; P=0.005), BAX (2.34 fold; P<0.001), BAK (1.29 fold; P=0.004), and BIM (1.4 fold; P<0.001) and downregulation of BCL-2 (0.44 fold; P<0.001), BCL-XL (0.47 fold; P<0.001), PI3K (P<0.001), AKT (P<0.001), and MTOR (P<0.001). Vipera raddei kurdistanica venom may exert selective cytotoxic effects against gastric cancer cells and may induce apoptosis through both intrinsic and extrinsic pathways, potentially via inhibition of the PI3K/AKT/mTOR signalling axis.

Emerging evidence demonstrates that Bcl-2/B cell lymphoma extra large (Bcl-xL)/myeloid cell leukemia 1 (Mcl-1) inhibitors (e.g., venetoclax and the derivatives) combined with p53/murine double minute 2 (MDM2) disruptors, epigenetic modifiers (e.g., histone deacetylase inhibitors), autophagy modulators, or kinases inhibitors, achieve synergistic potency. These rationally designed combination therapies effectively suppress compensatory upregulation of alternative anti-apoptotic proteins overcome Bcl-2/Bcl-xL/Mcl-1-driven resistance and restore drug efficacy in apoptosis-deficient cancer subtypes. This paradigm shift offers substantial potential to advance precision oncology by establishing durable responses through simultaneous blockade of multiple survival axes, and carries tremendous promise in the next-generation evolution of cancer therapeutics.

Etoposide was used as a reference in characterization, release, and loading studies...Plain liposomes exhibited minimal cytotoxicity, confirming their biocompatibility. Liposomal bromophenol, which we have introduced to the literature for the first time, is expected to be a promising nanocarrier system that could be effective in cancer treatment by improving the therapeutic index of new drug candidates such as marine bromophenols.

Among the synthesized compounds, the CuI complexes bearing triphenylphosphine co-ligands (compounds 4 and 5) exhibited the strongest cytotoxicity against U87 MG and LN18 GBM cell lines, showing IC50 values lower than those of cisplatin. Flow cytometry and Western blot analyses demonstrated that cell death occurs via caspase-dependent apoptosis in LN18 cells, as evidenced by PARP cleavage, downregulation of Bcl-xL, release of cytochrome c, and mitochondrial translocation of Bax. Altogether, these findings highlight the potential of lipophilic amantadine-functionalized CuI complexes as promising anticancer candidates targeting glioma cells through mitochondrial dysfunction and redox-mediated pathways.

These findings highlight a central role for CXCR2-mediated signaling in the development of radioresistance in HPV-negative HNSCC cells.

Moreover, a decline in reactive oxygen species generation by pretreatment of Wwox+/+ MEFs with an antioxidant N-acetyl-L-cysteine leads to decreased WWOX induction upon serum starvation. Taken together, our results suggest that stress stimuli trigger WWOX induction by elevating the production of reactive oxygen species in cells, which promotes the degradation of Bcl-XL and Mcl-1 proteins via a lysosome-mediated pathway, thereby further aggravating oxidative stress and cell death.

Collectively, these modulators demonstrate PPI druggability and provide chemical probes and lead scaffolds for therapeutic development in cancer, neurodegeneration, infectious disease, and immune disorders.

These results suggest that HST and Cisp co-treatment synergistically reduces cancer cell viability while protecting normal fibroblasts from senescence, supporting its potential as a co-chemotherapeutic agent in HCC treatment, while also serving as a protective agent against senescence in healthy tissues.