Blockade of transforming growth factor-β-activated kinase 1 activity enhances TRAIL-induced apoptosis through activation of a caspase cascade

Choo, Min‐Kyung; Kawasaki, Noritaka; Singhirunnusorn, Pattama; Koizumi, Keiichi; Sato, Shintaro; Akira, Shizuo; Saiki, Ikuo; Sakurai, Hiroaki

doi:10.1158/1535-7163.mct-06-0379

Cited by 42 publications

(40 citation statements)

References 45 publications

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“…Western blot analysis was performed as previously described (11). Cells were seeded and incubated overnight in a 60-mm culture dish (0.25x10 6 cells/ml).…”

Section: Methodsmentioning

confidence: 99%

Identification of plant extracts sensitizing breast cancer cells to TRAIL

et al. 2013

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Abstract. Triple-negative breast cancer (TNBC) is an aggressive heterogeneous cancer subgroup with a higher rate of distant recurrence and a poorer prognosis compared to other subgroups. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive molecule that induces cell death in various tumor cells without causing cytotoxicity to normal cells; however, primary or acquired resistance to TRAIL often limits its efficacy in cancer patients. To develop combination therapies to improve TRAIL efficacy and/or to overcome the resistant mechanism, we screened 138 medicinal plant extracts against TRAIL-sensitive and -insensitive TNBC cell lines, MDA-MB-231 and MDA-MB-468. Among them, 5 plant extracts, Uvaria dac, Artemisia vulgaris, Cortia depressa, Dichasia bengalensis and Cinnamomum obtusifolium did not cause apparent cytotoxicity (<20%) as a single regimen, but showed significant synergistic effects in combination with TRAIL against both cell lines. Moreover, Uvaria dac, Artemisia vulgaris and Cinnamomum obtusifolium were found to suppress the phosphorylation of p65 that is involved in TRAIL-resistant mechanisms. These observations suggest that the identified plant extracts in combination with TRAIL could lead to potential therapeutic benefits for cancer patients in the clinical setting. IntroductionBreast cancer is one of the most frequently diagnosed types of cancer and is also the leading cause of cancer-related mortality among women, representing 23% of total cancer cases and 14% of cancer-related mortality (1). Breast cancer is classified into different categories according to the expression of three receptors, estrogen receptor (ER), progesterone receptor (PR), and HER2/Neu (2). A triple-negative breast cancer (TNBC), which is ER-negative, PR-negative, and HER2-negative, is one of the most aggressive forms that accounts for 15-25% of all breast cancer cases and is associated with a poor prognosis and unresponsiveness to the usual endocrine therapies (3-5).The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can initiate apoptosis via the activation of death receptor 4 (DR4) and death receptor 5 (DR5). As TRAIL can selectively induce apoptosis in cancer cells, including breast cancer cells, without causing toxicity to normal cells (6-8), it could be a safe medication for cancer patients; however, primary or acquired resistance to TRAIL is often observed which may limit its efficacy in cancer patients (6). Therefore, increasing TRAIL efficacy by combining with natural medicines or other chemotherapeutic agents is an important strategy in the treatment of breast cancer in the clinical setting. We previously identified that vanillin, an active constituent of vanilla, enhances TRAIL-induced apoptosis in cancer cells via suppression of NF-κB (9). This finding prompted us to search for other natural products that can sensitize cancer cells to TRAIL or that can overcome the TRAIL-resistant mechanism.In the present study, we screened 138 medicin...

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“…Western blot analysis was performed as previously described (11). Cells were seeded and incubated overnight in a 60-mm culture dish (0.25x10 6 cells/ml).…”

Section: Methodsmentioning

confidence: 99%

Identification of plant extracts sensitizing breast cancer cells to TRAIL

et al. 2013

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“…TRAIL activated TAK1 in HeLa cells resulting in p65, JNK and p38 activation; siRNA knockdown or chemical inhibition of TAK1 enhanced TRAIL-induced apoptosis. 68 The earlier mentioned activation of p38 by TRAIL in prostate cancer cells was preceded and dependent on activation of TAK1, leading to transcriptional upregulation of Mcl-1 and suppression of apoptosis. 59 Inhibition of TAK1 is an effective approach to increase TRAIL sensitivity as was reported by Morioka et al 69 , although in their study, direct phosphorylation of TAK1 after TRAIL was not demonstrated.…”

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confidence: 96%

Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family

et al. 2013

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based therapy is currently evaluated in clinical studies as a tumor cell selective pro-apoptotic approach. However, besides activating canonical caspase-dependent apoptosis by binding to TRAIL-specific death receptors, the TRAIL ligand can activate non-canonical cell survival or proliferation pathways in resistant tumor cells through the same death receptors, which is counterproductive for therapy. Even more, recent studies indicate metastases-promoting activity of TRAIL. In this review, the remarkable dichotomy in TRAIL signaling is highlighted. An overview of the currently known mechanisms involved in non-canonical TRAIL signaling and the subsequent activation of various kinases is provided. These kinases include RIP1, IjB/ NF-jB, MAPK p38, JNK, ERK1/2, MAP3K TAK1, PKC, PI3K/Akt and Src. The functional consequences of their activation, often being stimulation of tumor cell survival and in some cases enhancement of their invasive behavior, are discussed. Interestingly, the non-canonical responses triggered by TRAIL in resistant tumor cells resemble that of TRAIL-induced signals in non-transformed cells. Better knowledge of the mechanism underlying the dichotomy in TRAIL receptor signaling may provide markers for selecting patients who will likely benefit from TRAIL-based therapy and could provide a rationalized basis for combination therapies with TRAIL death receptor-targeting drugs.

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“…We also performed experiments using the TAK1 inhibitor, 5Z-7-oxozeaenol. This compound is a resorcylic acid lactone of fungal origin, which has been shown to be a highly effective and specific inhibitor of TAK1 Choo et al, 2006). Pretreatment of cells with 5Z-7-oxozeaenol inhibited the phosphorylation of p38 (Fig.…”

Section: Resultsmentioning

confidence: 98%

Arsenic Trioxide-Dependent Activation of Thousand-and-One Amino Acid Kinase 2 and Transforming Growth Factor-β-Activated Kinase 1

McNeer

Goussetis²,

Sassano

et al. 2010

Mol Pharmacol

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Arsenic trioxide (As 2 O 3 ) has potent antileukemic properties in vitro and in vivo, but the mechanisms by which it generates its effects on target leukemic cells are not well understood. Understanding cellular mechanisms and pathways that are activated in leukemic cells to control the generation of As 2 O 3 responses should have important implications in the development of novel approaches using As 2 O 3 for the treatment of leukemias. In this study, we used immunoblotting and immune complex kinase assays to provide evidence that the kinases thousand-and-one amino acid kinase 2 (TAO2) and transforming growth factor-␤-activated kinase 1 (TAK1) are rapidly activated in response to treatment of acute leukemia cells with As 2 O 3 . Such activation occurs after the generation of reactive oxygen species and regulates downstream engagement of the p38 mitogen-activated protein kinase. Our studies demonstrate that siRNA-mediated knockdown of TAO2 or TAK1 or pharmacological inhibition of TAK1 enhances the suppressive effects of As 2 O 3 on KT-1-derived leukemic progenitor colony formation and on primary leukemic progenitors from patients with acute myelogenous leukemia. These results indicate key negative-feedback regulatory roles for these kinases in the generation of the antileukemic effects of As 2 O 3 . Thus, molecular or pharmacological targeting of these kinases may provide a novel approach to enhance the generation of arsenic-dependent antileukemic responses.

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Blockade of transforming growth factor-β-activated kinase 1 activity enhances TRAIL-induced apoptosis through activation of a caspase cascade

Cited by 42 publications

References 45 publications

Identification of plant extracts sensitizing breast cancer cells to TRAIL

Identification of plant extracts sensitizing breast cancer cells to TRAIL

Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family

Arsenic Trioxide-Dependent Activation of Thousand-and-One Amino Acid Kinase 2 and Transforming Growth Factor-β-Activated Kinase 1

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