Playing the DISC: Turning on TRAIL death receptor-mediated apoptosis in cancer

Pennarun, Bodvaël; Meijer, Annemieke; Vries, Elisabeth G.E. de; Kleibeuker, Jan H.; Kruyt, Frank A.E.; Jong, Steven de

doi:10.1016/j.bbcan.2009.11.004

Cited by 112 publications

(131 citation statements)

References 226 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…However, treatment with SAHA alone decreased the level of the anti-apoptotic factor c-FLIP. Because c-FLIP prevents the activation of procaspase-8 at the DISC [51], its down-regulation was responsible for activation of caspase-8. Such an effect became more consistent when the cells were treated with SAHA/TRAIL combination.…”

Section: Discussionmentioning

confidence: 99%

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

et al. 2012

View full text Add to dashboard Cite

a b s t r a c t SAHA, an inhibitor of histone deacetylase activity, has been shown to sensitize tumor cells to apoptosis induced by TRAIL, a member of TNF-family. In this paper we investigated the effect of SAHA/TRAIL combination in two breast cancer cell lines, the ERaÀpositive MCF-7 and the ERaÀnegative MDA-MB231. Treatment of MDA-MB231 and MCF-7 cells with SAHA in combination with TRAIL caused detachment of cells followed by anoikis, a form of apoptosis which occurs after cell detachment, while treatment with SAHA or TRAIL alone did not produce these effects. The effects were more evident in MDA-MB231 cells, which were chosen for ascertaining the mechanism of SAHA/TRAIL action. Our results show that SAHA decreased the level of c-FLIP, thus favouring the interaction of TRAIL with the specific death receptors DR4 and DR5 and the consequent activation of caspase-8. These effects increased when the cells were treated with SAHA/TRAIL combination. Because z-IEDT-fmk, an inhibitor of caspase-8, prevented both the cleavage of the focal adhesion-kinase FAK and cell detachment, we suggest that activation of caspase-8 can be responsible for both the decrement of FAK and the consequent cell detachment. In addition, treatment with SAHA/TRAIL combination caused dissipation of DJ m , activation of caspase-3 and decrement of both phospho-EGFR and phospho-ERK1/2, a kinase which is involved in the phosphorylation of BimEL. Therefore, co-treatment also induced decrement of phospho-BimEL and a concomitant increase in the dephosphorylated form of BimEL, which plays an important role in the induction of anoikis.Our findings suggest the potential application of SAHA in combination with TRAIL in clinical trials for breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

SAHA/TRAIL combination induces detachment and anoikis of MDA-MB231 and MCF-7 breast cancer cells

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Among the many immune factors, the TRAIL is known to induce cellular apoptosis [1]. Recently, TRAIL has received primal attention due to its ability to recognize and induce apoptosis of tumors and metastases while leaving normal cells unscathed.…”

Section: Purposementioning

confidence: 99%

“…Over the last decade, the search to induce apoptosis (programmed cell death) in cancer cells have led to the emergence of a new and fast growing field termed cancer immunology. Here, the interactions between immune system with malignant cancers have shown the suppression of the disease progression [1].…”

Section: Purposementioning

confidence: 99%

Signaling Flux Redistribution concept can switch survival to apoptosis in cancer cells

et al. 2010

View full text Add to dashboard Cite

The tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induces apoptosis in certain types of carcinoma. However, in majority of malignant tumors, it has no effect. Here we analyzed cell survival and apoptotic pathways triggered by TRAIL. A computational model based on perturbation-response approach with mass-action equations was developed. All 48 parameter values of the model were selected by genetic algorithm that minimizes deviation between experimental and simulation data for human fibrosarcoma cells. Subsequently, we show in silico knock-down of a cell survival pathway molecule could potentially enhance the activation of apoptosis through Signaling Flux Redistribution (SFR).

show abstract

“…An example of apoptosome is the FasL−Fas−FADD−procaspase-8 complex, in which caspase-8 is activated (Figure 3) [7,21]. Death receptors can mediate activation of caspases-2; -8, and -10 [22]. The activated initiator caspases then activate effector caspases.…”

Section: Bodymentioning

confidence: 99%