Bcl-2 Family Members as Sentinels of Cellular Integrity and Role of Mitochondrial Intermembrane Space Proteins in Apoptotic Cell Death

Festjens, Nele; Gurp, Maria van; Loo, Geert; Saelens, Xavier; Vandenabeele, Peter

doi:10.1159/000074483

Cited by 96 publications

(68 citation statements)

References 180 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The Bcl-2 family consists of more than 30 proteins, which can be divided into three subgroups: Bcl-2-like survival factors, Bax-like death factors, and BH 3 -only death factors. Residues from BH1, 2, and 3 form a hydrophobic groove, with which BH 3 -only death factors interact through their BH 3 -domain, whereas the N-terminal BH 4 -domain stabilizes this pocket (Festjens et al, 2004).…”

Section: Apoptosis and Crcmentioning

confidence: 99%

Dietary Non-nutritive Factors in Targeting of Regulatory Molecules in Colorectal Cancer: An Update

Pandurangan

Esa²

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Colorectal cancer (CRC), a complex multi-step process involving progressive disruption of homeostatic mechanisms controlling intestinal epithelial proliferation/inflammation, differentiation, and programmed cell death, is the third most common malignant neoplasm worldwide. A number of promising targets such as inducible nitric acid (iNOS), cyclooxygenase (COX)-2, NF-E2-related factor 2 (Nrf2), Wnt/β-catenin, Notch and apoptotic signaling have been identified by researchers as useful targets to prevent or therapeutically inhibit colon cancer development. In this review article, we aimed to explore the current targets available to eliminate colon cancer with an update of dietary and non-nutritional compounds that could be of potential use for interaction with regulatory molecules to prevent CRC.

show abstract

Section: Apoptosis and Crcmentioning

confidence: 99%

Dietary Non-nutritive Factors in Targeting of Regulatory Molecules in Colorectal Cancer: An Update

Pandurangan

Esa²

2013

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

show abstract

“…The mitochondrial pathway of apoptosis is dependent on the process of mitochondrial outer membrane permeabilization. Midochondrial based apoptosis can be stimulated by caspase dependent and caspase independent pathways and is regulated by members of Bcl-2 family [26][27][28]. Results of this study show that curcumin downregulated antiapoptotic Bcl-2 and MGN-3 upregulated proapoptotic Bax of U266 cells.…”

Section: Discussionmentioning

confidence: 66%

Synergistic apoptotic effect of Arabinoxylan rice bran (MGN-3/Biobran) and Curcumin (Turmeric) on human multiple myeloma cell line U266 in vitro

Ghoneum¹,

Gollapudi²

2011

neo

View full text Add to dashboard Cite

The present study was carried out to investigate the synergistic apoptotic potential of arabinoxylan rice bran (MGN-3/Biobran) and curcumin (turmeric) on human multiple myeloma (MM) cell line U266 , in vitro. U266 cells were cultured with MGN-3 (50 or 100μg/ml) and curcumin (2.5-10μM) for 3 days. The effects of MGN-3 and curcumin on the growth and survival of the U266 cells were determined by trypan blue, MTT assay, flow cytometry analysis of cancer cell cycle, and apoptosis. Expression of proapoptotic Bax, and antiapoptotic Bcl2 was determined by Western blot analysis. Treatment with MGN-3 alone or curcumin alone caused a dose-dependent inhibition in the proliferation of U266 cells. However, a synergistic effect was noticed post-treatment with both agents that maximized at 100μg/ml MGN-3 plus 10μM curcumin. This synergy was characterized by an 87% decrease in cell number and a 2.6 fold increase in the percentage of apoptotic U266 cells. Cell cycle analysis showed a 53% decrease in the percentage of cells in the G0-G1 phase treated with MGN-3 and curcumin (from 36% to 17%). Analysis of the expression of the pro and antiapoptotic molecules Bax and Bcl-2 revealed synergistic effects of these agents, as the expression of Bcl-2 was decreased and Bax was increased. This resulted in a cellular microenvironment favorable for apoptosis. We conclude that MGN-3 and curcumin synergize in the induction of U266 cell apoptosis. This data may establish the foundation for in vivo studies that could have therapeutic implications.

show abstract

“…Activated Akt phosphorylates the intracellular protein Bad, resulting in the release of the anti-apoptotic protein Bcl-2, which contributes to cancer cell survival. Bax, a dominant-negative inhibitor of Bcl-2, induces a mitochondrial permeability transition and promotes apoptosis [33]. Caspase-3 acts as a final executor in apoptosis and can be irreversibly activated through cleavage of pro-caspase-3 [34].…”

Section: Effect Of 11a On Apoptosis-related Proteinsmentioning

confidence: 99%

Discovery of novel antitumor nitric oxide-donating β -elemene hybrids through inhibiting the PI3K/Akt pathway

Chen

Wang

et al. 2017

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

A series of novel furoxan-based NO-donating β-elemene hybrids were designed and synthesized to improve the anticancer efficacy of natural β-elemene. The bioassay results indicated that all of the target compounds exhibited significantly improved antiproliferative activities against three cancer cell lines (SGC-7901, HeLa and U87) compared to parent compound β-elemene. Interestingly, these compounds displayed excellent sensitivity to U87 cells with IC50 values ranging from 173 to 2 nM. Moreover, most compounds produced high levels of NO in vitro, and the antitumor activity of 11a in U87 cells was markedly attenuated by an NO scavenger (hemoglobin or carboxy-PTIO). Further mechanism studies revealed that 11a caused the G2 phase arrest of the cell cycle and induced apoptosis of U87 cells by preventing the activation of the PI3K/Akt pathway. Moreover, 11a significantly suppressed the tumor growth in H22 liver cancer xenograft mouse model with a tumor inhibitory ratio (TIR) of 64.8%, which was superior to that of β-elemene (TIR, 49.6%) at the same dose of 60 mg/kg. Together, the remarkable biological profiles of these novel NO-donating β-elemene derivatives may make them promising candidates for the intervention of human cancers.

show abstract

Bcl-2 Family Members as Sentinels of Cellular Integrity and Role of Mitochondrial Intermembrane Space Proteins in Apoptotic Cell Death

Cited by 96 publications

References 180 publications

Dietary Non-nutritive Factors in Targeting of Regulatory Molecules in Colorectal Cancer: An Update

Dietary Non-nutritive Factors in Targeting of Regulatory Molecules in Colorectal Cancer: An Update

Synergistic apoptotic effect of Arabinoxylan rice bran (MGN-3/Biobran) and Curcumin (Turmeric) on human multiple myeloma cell line U266 in vitro

Discovery of novel antitumor nitric oxide-donating β -elemene hybrids through inhibiting the PI3K/Akt pathway

Contact Info

Product

Resources

About