TNF-related apoptosis-inducing ligand (TRAIL) as the potential therapeutic target in hematological malignancies

Naimi, Adel; Movassaghpour, Ali Akbar; Hagh, Majid Farshdousti; Talebi, Mehdi; Entezari, Atefeh; Jadidi‐Niaragh, Farhad; Solali, Saeed

doi:10.1016/j.biopha.2017.12.082

Cited by 35 publications

(29 citation statements)

References 152 publications

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“…for cancer. 37,38 Our ex vivo coculture experiment reveals that TRAIL induces apoptosis of leukocytes during desiccating stress as evidenced by reduced frequency of annexin V + apoptotic immune cell in DED-LGs following neutralization of soluble TRAIL. Furthermore, our gain-of-function approach demonstrates that supplementation of recombinant TRAIL in TRAIL-deficient cultures of HIF-1α CKO LG significantly promotes immune cell apoptosis following DED.…”

Section: Discussionmentioning

confidence: 88%

HIF1α-mediated TRAIL Expression Regulates Lacrimal Gland Inflammation in Dry Eye Disease

Lee

Choi

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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The purpose of this study was to investigate the expression of death ligands in the lacrimal glands (LGs), identify upstream factors that regulate their expression, and determine the functional roles of these factors in the pathogenesis of dry eye disease (DED). METHODS. For DED experiment, ex vivo coculture system with LG and in vivo murine model using a controlled environment chamber were utilized. C57BL/6 mice and hypoxiainducible factor (HIF)-1α conditional knockout (CKO) mice were used. Immunohistochemical staining, polymerase chain reaction, and immunoblotting were performed to determine levels of death ligands including tumor necrosis factor-related apoptosisinducing ligand (TRAIL) in DED-induced LGs. Additionally, acinar cell and CD45 + cell apoptosis was determined with neutralizing TRAIL treatment. RESULTS. Desiccating stress significantly increased HIF-1α expression in LG-acinar cells. Furthermore, HIF-1α deficiency significantly enhanced the infiltration of CD45 + inflammatory cells in LG and induced LG-acinar cell death. Meanwhile, only TRAIL expression was increased in DED-LG, but abrogated in HIF-1α CKO. Interestingly, the main source of TRAIL was the CD45-LG-acinar cells, but not CD45 + immune cells after DED induction. Using ex vivo coculture system, we confirmed LG-induced apoptosis of immune cells via HIF-1α-mediated TRAIL secretion following DED. Consistent with ex vivo, the insufficiency of HIF-1α and TRAIL enhanced recruitment of inflammatory cells to the LG and subsequently exacerbated ocular surface damage in DED mice. CONCLUSIONS. Our findings offer novel insight into the regulatory function of acinar cellderived TRAIL in limiting inflammatory damage and could be implicated in the development of potential therapeutic strategies for DED.

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Section: Discussionmentioning

confidence: 88%

HIF1α-mediated TRAIL Expression Regulates Lacrimal Gland Inflammation in Dry Eye Disease

Lee

Choi

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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“…In fact, TRAIL showed only few side effects in clinical trials. However, the clinical efficacy of TRAIL monotherapy was also limited [64,65,66,67].…”

Section: Critical Role Of Apoptosis Deficiency In Melanomamentioning

confidence: 99%

Countering TRAIL Resistance in Melanoma

Eberle

2019

Cancers

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Melanoma of the skin has become a prime example for demonstrating the success of targeted cancer therapy. Nevertheless, high mortality has remained, mainly related to tumor heterogeneity and inducible therapy resistance. But the development of new therapeutic strategies and combinations has raised hope of finally defeating this deadly disease. TNF-related apoptosis-inducing ligand (TRAIL) represents a promising antitumor strategy. The principal sensitivity of melanoma cells for TRAIL was demonstrated in previous studies; however, inducible resistance appeared as a major problem. To address this issue, combination strategies were tested, and survival pathway inhibitors were shown to sensitize melanoma cells for TRAIL-induced apoptosis. Finally, cell cycle inhibition was identified as a common principle of TRAIL sensitization in melanoma cells. Mitochondrial apoptosis pathways, pro- and antiapoptotic Bcl-2 proteins as well as the rheostat consisted of Smac (Second mitochondria-derived activator of caspase) and XIAP (X-linked inhibitor of apoptosis protein) appeared to be of particular importance. Furthermore, the role of reactive oxygen species (ROS) was recognized in this setting. Inducible TRAIL resistance in melanoma can be explained by (i) high levels of antiapoptotic Bcl-2 proteins, (ii) high levels of XIAP, and (iii) suppressed Bax activity. These hurdles have to be overcome to enable the use of TRAIL in melanoma therapy. Several strategies appear as particularly promising, including new TRAIL receptor agonists, Smac and BH3 mimetics, as well as selective kinase inhibitors.

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“…TRAIL is an alternative antitumor agent that induces apoptosis in a variety of cancer cell types without cytotoxic effect in normal cells and therefore represents a promising novel target for antitumor therapeutics. 29 However, many studies indicated that many types of cancer are resistant to the antitumor effects of TRAIL. 43 Therefore, developing drugs that sensitize cancer cells to TRAIL-mediated antitumor activity is important to improve the therapeutic efficacy of TRAIL.…”

Section: Discussionmentioning

confidence: 99%

“…28 Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, also known as apo2 ligand) is a cytokine the has no effect on normal cells, but the ability of which to selectively induce apoptosis in cancer cells is well known. 29 TRAIL binds to cell surface death receptor 4 (DR4; TRAIL-R1) or death receptor 5 (DR5; TRAIL-R2), which further recruit the adaptor Fas-associated protein with death domain (FADD) and caspase 8, leading to the activation of caspase 3. 30,31 In the current study, our findings demonstrated that ixazomib sensitizes TRAIL-induced apoptosis via CHOPdependent DR5 induction.…”

Section: Introductionmentioning

confidence: 99%

Ixazomib promotes CHOP-dependent DR5 induction and apoptosis in colorectal cancer cells

Yue

Sun

2018

Cancer Biology & Therapy

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Background: Ixazomib (Ninlaro), a novel proteasome inhibitor, has been developed for the treatment of many cancers and has demonstrated anti-tumor efficacy against various malignancies. However, the mechanism of the anti-tumor effect of ixazomib in colorectal cancer (CRC) cells remains unclear. Methods: MTS and flow cytometry were performed to determine the effect of ixazomib on CRC cells. Western blotting and real-time RT-PCR were performed to detect ixazomib-induced DR5 upregulation. ChIP was performed to detect CHOP binding to DR5 promoter. Finally, xenograft experiments were carried out to measure the antitumor effect of ixazomib in vivo. Results: In this study, we revealed the mechanism by which ixazomib inhibits the growth of CRC cells. Our findings indicated that ixazomib treatment induces CHOP-dependent DR5 induction, irrespective of p53 status. Furthermore, DR5 is necessary for ixazomib-mediated apoptosis. Ixazomib also synergized with TRAIL to induce marked apoptosis via DR5 in CRC cells. Conclusions: Our findings further suggested that ixazomib sensitizes TRAIL/death receptor signaling pathway-targeted CRC and suggested that DR5 induction could be a valuable indicator of ixazomib sensitivity.

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TNF-related apoptosis-inducing ligand (TRAIL) as the potential therapeutic target in hematological malignancies

Cited by 35 publications

References 152 publications

HIF1α-mediated TRAIL Expression Regulates Lacrimal Gland Inflammation in Dry Eye Disease

HIF1α-mediated TRAIL Expression Regulates Lacrimal Gland Inflammation in Dry Eye Disease

Countering TRAIL Resistance in Melanoma

Ixazomib promotes CHOP-dependent DR5 induction and apoptosis in colorectal cancer cells

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