Mechanisms of enhancement of TRAIL tumoricidal activity against human cancer cells of different origin by dipyridamole

Goda, Ahmed E.; Yoshida, Tatsushi; Horinaka, Mano; Yasuda, Takashi; Shiraishi, Takeshi; Wakada, Miki; Sakai, Toshiyuki

doi:10.1038/sj.onc.1211008

Cited by 22 publications

(17 citation statements)

References 33 publications

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“…It has been documented that some TZD decrease c‐FLIP39 or survivin expression,32, 40, 41 which contributes to enhancement of TRAIL‐induced apoptosis in certain types of cancer cells. We demonstrated that survivin expression is reduced in case of apoptosis or cell cycle arrest induction after TZD treatment.…”

Section: Discussionmentioning

confidence: 99%

Insights on distinct pathways of thiazolidinediones (PPARγ ligand)‐promoted apoptosis in TRAIL‐sensitive or ‐resistant malignant urothelial cells

Plissonnier

Fauconnet

Bittard

et al. 2010

Intl Journal of Cancer

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Thiazolidinediones, including rosiglitazone and troglitazone, are insulin-sensitizing drugs and high-affinity ligands for the peroxisome proliferator-activated receptor c (PPARc). Apart from their antidiabetic activity, these molecules possess antitumor properties. We investigated their potential apoptotic effects on RT4 (derived from a well-differentiated Grade I papillary tumor) and T24 (derived from an undifferentiated Grade III carcinoma) bladder cancer cells. Rosiglitazone induced G2/M or G0/G1 phase cell cycle arrest in RT4 and T24 cells, respectively. Only troglitazone triggered apoptosis via extrinsic and intrinsic pathways in both cell lines. Interestingly, rosiglitazone amplified TRAIL-induced apoptosis in TRAIL-sensitive RT4 cells or let TRAIL-resistant T24 cells to respond to TRAIL. Thiazolidinediones acted through PPARc activation-independent mechanisms. The underlying mechanisms involved for the first time in cancer cells the upregulation of soluble and/or membrane-bound TRAIL. This was associated with increased cell surface death receptor 5 expression and c-FLIP and survivin downregulation, mediated in part through proteasome-dependent degradation in troglitazone-promoted cell death. Therefore, the combination of rosiglitazone and TRAIL could be clinically relevant as chemopreventive or therapeutic agents for the treatment of TRAILresistant high-grade urothelial cancers.Bladder cancer accounts for $5% of all cancer deaths in humans. Despite the advances with intravesical immuno-and chemotherapy, surgery and systemic chemotherapy in the management of patients and although new cytotoxic chemotherapeutic agents for either advanced or metastatic bladder cancer are used, no improvement in survival has been observed. Thus, targeted therapy with novel agents is a promising avenue to improve patient outcome.Thiazolidinediones (TZD), including rosiglitazone and troglitazone, are a class of insulin-sensitizing drugs. Besides, rosiglitazone is currently in clinical use for the treatment of type II diabetes.1,2 These TZD are high-affinity chemically synthesized ligands for the peroxisome proliferator-activated receptor c (PPARc).3 PPARc is a ligand-activated transcription factor of the nuclear hormone receptor superfamily. In addition to its known role in regulation of metabolism and inflammation, PPARc has also been implicated in carcinogenesis based on studies showing its ability to modulate cellular differentiation, proliferation and apoptosis. Apart from their antidiabetic activity, TZD elicit growth inhibitory effects in vitro on cancer cells of diverse tissue origins and in vivo. Few studies indicate that certain TZD members exhibited antiproliferative or proapoptotic activities against a broad spectrum of bladder cancer cell lines.5-8 Thus, treatment of the T24 bladder cancer cells with troglitazone induced G0/G1 cell cycle arrest and cell death.5 In addition, depending on TZD member, the induction of apoptosis is PPARc-dependent or -independent. 9 Interestingly, TZD could sensitize tumor cells to TRAI...

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Section: Discussionmentioning

confidence: 99%

Insights on distinct pathways of thiazolidinediones (PPARγ ligand)‐promoted apoptosis in TRAIL‐sensitive or ‐resistant malignant urothelial cells

Plissonnier

Fauconnet

Bittard

et al. 2010

Intl Journal of Cancer

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“…Additionally, 2–14 promotes the proteasome-mediated degradation of survivin, a major hurdle to TRAIL signaling in these CRC cell lines [69]. Both CHOP-mediated DR5 increase and survivin down-regulation are also the major mechanisms by which dipyridamole, a thromboxane synthase inhibitor widely used as an antiplatelet, sensitizes SW480 cells to TRAIL [70]. …”

Section: Trail-sensitizing Agents In Crcmentioning

confidence: 99%

Molecular Targets of TRAIL-Sensitizing Agents in Colorectal Cancer

Stolfi

Pallone

Monteleone

2012

IJMS

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Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily, interacts with its functional death receptors (DRs) and induces apoptosis in a wide range of cancer cell types. Therefore, TRAIL has been considered as an attractive agent for cancer therapy. However, many cancers are resistant to TRAIL-based therapies mainly due to the reduced expression of DRs and/or up-regulation of TRAIL pathway-related anti-apoptotic proteins. Compounds that revert such defects restore the sensitivity of cancer cells to TRAIL, suggesting that combined therapies could help manage neoplastic patients. In this article, we will focus on the TRAIL-sensitizing effects of natural products and synthetic compounds in colorectal cancer (CRC) cells and discuss the molecular mechanisms by which such agents enhance the response of CRC cells to TRAIL.

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“…The XIAP, surviving, and LacZ siRNA were described previously (25,26) and synthesized by Proligo. GLO1 siRNA was purchased from Santa Cruz Biotechnology.…”

Section: Sirnasmentioning

confidence: 99%

Targeting the Glyoxalase Pathway Enhances TRAIL Efficacy in Cancer Cells by Downregulating the Expression of Antiapoptotic Molecules

Taniguchi

Horinaka

Yoshida

et al. 2012

Molecular Cancer Therapeutics

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Methylglyoxal is an essential component in glycolysis and is known to be an inducer of apoptosis. Glyoxalase I (GLO1) metabolizes and inactivates methylglyoxal. GLO1 is known to be overexpressed in cancer cells and causes resistance to anticancer agents. We show for the first time that methylglyoxal treatment or the silencing of GLO1 enhances sensitivity to the promising anticancer agent TRAIL in malignant tumor cells. Methylglyoxal suppressed the expression of antiapoptotic factors, X-linked inhibitor of apoptosis protein (XIAP), survivin, cIAP1, Bcl-2, and Bcl-xL, without affecting TRAIL receptors, DR4 and DR5. Knockdown of XIAP or survivin by siRNA also enhanced TRAIL-induced apoptosis, indicating that downregulation of XIAP and survivin expression by methylglyoxal contributes to the enhancement of TRAIL activity. Furthermore, methylglyoxal decreased NF-kB activity with or without TRAIL treatment. On the other hand, the knockdown of GLO1 by siRNA enhanced TRAIL-induced apoptosis via the downregulation of XIAP and survivin expression. In conclusion, our results strongly suggest that sensitivity to TRAIL is increased by inhibition of the glyoxalase pathway and that the combination of TRAIL with methylglyoxal or glyoxalase inhibitors may be useful for a novel combination chemotherapy. Mol Cancer Ther; 11(10); 2294-300. Ó2012 AACR.

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Mechanisms of enhancement of TRAIL tumoricidal activity against human cancer cells of different origin by dipyridamole

Cited by 22 publications

References 33 publications

Insights on distinct pathways of thiazolidinediones (PPARγ ligand)‐promoted apoptosis in TRAIL‐sensitive or ‐resistant malignant urothelial cells

Insights on distinct pathways of thiazolidinediones (PPARγ ligand)‐promoted apoptosis in TRAIL‐sensitive or ‐resistant malignant urothelial cells

Molecular Targets of TRAIL-Sensitizing Agents in Colorectal Cancer

Targeting the Glyoxalase Pathway Enhances TRAIL Efficacy in Cancer Cells by Downregulating the Expression of Antiapoptotic Molecules

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