Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy?

Kulsoom, Bibi; Shamsi, Tahir; Afsar, Nasir Ali; Memon, Zahida; Ahmed, Nikhat; Hasnain, S. N.

doi:10.2147/cmar.s154608

Cited by 121 publications

(103 citation statements)

References 43 publications

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“…Two proteins located in 5 cytoplasm of the cells, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2, are the activator and an inhibitor of apoptosis, respectively. It has been described, that Bax and Bcl-2, and their ratio, are predictive markers in different cancers [8]. Also, the significance of other molecules included in the apoptosis, such as caspases, had also been previously reported [9].…”

Section: Introductionmentioning

confidence: 88%

New gold pincer-type complexes induce caspase-dependent apoptosis in human cancer cells in vitro

et al. 2021

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Background / Aim. We investigated cytotoxicity of Au(III) complexes with pincer type ligands against cervical carcinoma cells (HeLa), breast cancer cells (MDA-MB-231 and 4T1) and colon carcinoma cells (HCT116 and CT26). We also examined the type and mechanism of cell death that these complexes induced in cancer cells. Methods.Cytotoxicity of Au(III) complexes was investigated by MTT assay. Apoptosis of treated cancer cells was measured by flow cytometry and applying Annexin V/7AAD staining. The expressions of active proapoptotic protein Bax, antiapoptotic protein Bcl-2 and the percentage of cells containing cleaved caspase-3 in treated cancer cells was determined by flow cytometry. Results. Complex 1 showed the most potent anti-tumor effect on HeLa cells, both compared to other two examined gold complexes and compared to cisplatin. The IC50 values on HeLa cells after 72 hours were 1.3 ± 0.4 μM, 3.4 ± 1.3 μM, 5.7 ± 0.6 μM, 26.7 ± 6.5 μM for complexes 1, 2, 3 and cisplatin, respectively. Complex 1 also exhibited highest cytotoxicity against MDA-MB-231 and HCT116 cells compared to other tested compounds. The results of Annexin V/7AAD staining showed that all three complexes induced apoptosis in treated cells. Our gold(III) complexes induced apoptosis by caspasedependent mechanism, but we did not observe that an activation of the internal pathway of apoptosis occurred in treated cancer cells. Conclusion. According to the results of our in vitro study, all three compounds and especially complex 1 are promising candidates for a new generation of anticancer drugs. Uvod. Ispitivali smo citotoksičnost Au(III) kompleksa sa ligandima tipa pincer protiv ćelija karcinoma grlića materice (HeLa), ćelija raka dojke (MDA-MB-231 i 4T1) i ćelija karcinoma kolona (HCT116 i CT26). TakoĎe smo ispitali tip i mehanizam ćelijske smrti koji su ovi kompleksi indukovani u ćelijama raka. Metode. Citotoksičnost Au(III) kompleksa je ispitivana pomoću MTT testa. Apoptoza tretiranih ćelija raka je merena protočnom citometrijom i primenom bojenja Aneksin V/7AAD. Ekspresija aktivnog proapoptotičnog proteina Bax, antiapoptotskog proteina Bcl-2 i procenat ćelija koje sadrže aktivnu kaspazu-3 u tretiranim ćelijama raka je odreĎena protočnom citometrijom. Rezultati. Kompleks 1 je pokazao najsnažniji antitumorski efekat na HeLa ćelije, kako u 4 poreĎenju sa drugim ispitivanim kompleksima zlata, tako i u poreĎenju sa cisplatinom.Vrednosti IC50 kompleksa zlata na HeLa ćelije nakon 72 sata bile su 1,3 ± 0,4 μM, 3,4 ± 1,3 μM, 5,7 ± 0,6 μM, 26,7 ± 6,5 μM za komplekse 1, 2, 3 i cisplatin. Kompleks 1 je takoĎe pokazao najvišu citotoksičnost prema MDA-MB-231 i HCT116 ćelijama u poreĎenju sa drugim testiranim jedinjenjima. Rezultati bojenja aneksinomV/7AAD pokazali su da sva tri kompleksa indukuju apoptozu u tretiranim ćelijama. Naši kompleksi zlata(III) indukovali su apoptozu mehanizmom koji je zavisio od kaspaze, ali nismo pokazali da je u tretiranim ćelijama raka došlo do aktivacije unutrašnjeg puta apoptoze. Zakljuĉak. Prema rezultatima naše in vitro studij...

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Section: Introductionmentioning

confidence: 88%

New gold pincer-type complexes induce caspase-dependent apoptosis in human cancer cells in vitro

et al. 2021

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“…The bcl-2 protein is located in the endoplasm momentum and mitochondrial membranes, and it can inhibit the release of apoptosis-inducing factors to prevent cell apoptosis. In apoptosis, Bax protein activates the cascade of reactions by releasing cytochrome c from the mitochondria that helps in successive activation of caspases and ultimately leads to cell death [27]. Let-7b was noted to induce apoptosis of LECs through targeting leucine-rich repeat containing G protein-coupled receptor 4 (Lgr4) [26].…”

Section: Introductionmentioning

confidence: 99%

Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells

Huang

Zhou

et al. 2020

BioMed Research International

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Background. Oxidative stress is an important factor during age-related cataract formation. Apoptosis and autophagy induced by oxidative stress have been reported as key factors in age-related cataract. In our research, we investigated the role of let-7c-3p in the regulation of autophagy and apoptosis during the formation of age-related cataract. Material and Methods. Real-time PCR and western blot were employed to detect the expression of let-7c-3p in the tissues of age-related cataract. Human lens epithelial cells (LECs) were treated with H2O2 as an age-related cataract model. The extent of apoptosis was measured by flow cytometry and western blot. To detect autophagy, immunofluorescence was used to analyze the spot number of LC3, and western blot was used to detect the expression of LC3-II/I and ATG3. The molecular mechanisms of let-7c-3p regulating autophagy via ATG3 under oxidative stress were performed by a luciferase report gene assay and rescue experiment. Results. Downregulation of let-7c-3p was found in the age-related cataract group aged >65 years relative to the age-related cataract group aged ≤65 years. Consistently, the expression of let-7c-3p was also lower under oxidative stress. The activities of LEC apoptosis and autophagy induced by oxidative stress were inhibited by let-7c-3p. By the bioinformatics database and the luciferase reporter assay, ATG3 was found to be a direct target of let-7c-3p. Let-7c-3p reduced the ATG3-mediated autophagy level, which was induced by oxidative stress in LECs. Conclusion. Let-7c-3p inhibits autophagy by targeting ATG3 in LECs in age-related cataract.

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“…Our findings revealed an increase in expression of Bax and a decrease in Bcl-2 genes when hBMSCs were treated with 5 ng/mL of Feijoa until day 7 th in comparison to the control group illustrating that Bax and Bcl-2 play important roles in apoptosis and cell proliferation (8,(24)(25)(26)(27). Bcl-2 was shown to have two classes of pro-apoptotic (Bax, Bad, Bid, Bik) and anti-apoptotic proteins (Bcl-2, Bcl-XL, Bcl-W).…”

Section: Discussionmentioning

confidence: 69%

Screening of Feijoa (Acca Sellowiana (O. Berg) Burret) Fruit Effect on Proliferation and Apoptosis using Bone Marrow derived Stem Cells Model

et al. 2020

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Background and Objective: Curative properties of Feijoa sellowiana Bert. (Myrtaceae, Acca sellowiana), have been often claimed, while investigations into details of its bioactivities are still lacking. This study investigated the effect of acetonic extract of Feijoa (Acca sellowiana (O. Berg) Burret) fruit on proliferation and apoptosis of bone marrow derived stem cells. Methodology: Human bone marrow stem cells (hBMSCs) were characterized before experiments. MTT Assay was performed to determine the toxicity of Feijoa. The growth kinetics was also investigated until 7 days. Real time PCR assessed the expression of apoptosis genes. Results: In MTT assay, Feijoa at doses ≤ 5 ng/ml did not show any cytotoxic effect on hBMSCs and increased the cell proliferation until day 4 th followed by a decrease until day 7 th. Population doubling time (PDT) decreased until day 4 th followed by an increase until day 7 th. A significant increase in expression of Bax and decrease Bcl-2 expression were recorded on day 7 th. Conclusion: The antioxidant, anti-inflammatory and modulatory activities of Feijoa can explain the increasing effect on cell proliferation till day 4 th , but the apoptotic activity of Feijoa noted after four days is reported for the first time denoting to the short term antioxidant, anti-inflammatory and modulatory properties of Feijoa that should be considered for curative activity of this fruit.

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Bax, Bcl-2, and Bax/Bcl-2 as prognostic markers in acute myeloid leukemia: are we ready for Bcl-2-directed therapy?

Cited by 121 publications

References 43 publications

New gold pincer-type complexes induce caspase-dependent apoptosis in human cancer cells in vitro

New gold pincer-type complexes induce caspase-dependent apoptosis in human cancer cells in vitro

Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells

Screening of Feijoa (<i>Acca Sellowiana</i> (<i>O. Berg</i>) <i>Burret</i>) Fruit Effect on Proliferation and Apoptosis using Bone Marrow derived Stem Cells Model

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