Azadirone, a Limonoid Tetranortriterpene, Induces Death Receptors and Sensitizes Human Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) through a p53 Protein-independent Mechanism

Gupta, Subash C.; Francis, Sajin K.; Nair, Mangalam S.; Mo, Yin Yuan; Aggarwal, Bharat B.

doi:10.1074/jbc.m113.455188

Cited by 57 publications

(51 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous work, curcumin enhanced the expression of JNK [9], this may account for the activated ERK. Sustained activation of ERK was also related to the apoptosis induction in some anti-cancer drugs [18]. U0126, an ERK inhibitor, abolished curcumin-induced DNA ladder, indicating that the activation of ERK was responsible for the induction of apoptosis.…”

Section: Journal Of Asian Natural Products Researchmentioning

confidence: 98%

Ras/ERK signaling pathway is involved in curcumin-induced cell cycle arrest and apoptosis in human gastric carcinoma AGS cells

Tang

Zhou

et al. 2014

Journal of Asian Natural Products Research

View full text Add to dashboard Cite

Curcumin, the biologically active compound from the rhizome of Curcuma longa, could inhibit cell growth and induce apoptosis in gastric carcinoma. However, the underlying mechanism of curcumin on gastric carcinoma cells still needs further investigation. In this study, morphological observation indicated that curcumin inhibited the proliferation of AGS cells in a dose-dependent manner. According to the flow cytometric analysis, curcumin treatment resulted in G2/M arrest in AGS cells, accompanied with an increased expression of cyclin B1 and a decreased expression of cyclin D1. In addition, DNA ladders were observed by gel electrophoresis. Meanwhile, the activities of caspase-3, -8, and -9 were also enhanced in curcumin-treated AGS cells. Nevertheless, the increased activities could be inhibited by benzyloxycarbonyl-Val-Ala-Asp (OME)-fluoromethylketone (z-VAD-fmk), which suggested that the apoptosis was caspase-dependent. Furthermore, downregulation of rat sarcoma (Ras) and upregulation of extracellular-signal-regulated kinase (ERK) were also observed in AGS cells treated with curcumin by Western blot. U0126, an ERK inhibitor, blocked curcumin-induced apoptosis. The results suggested that curcumin inhibited the growth of the AGS cells and induced apoptosis through the activation of Ras/ERK signaling pathway and downstream caspase cascade, and curcumin might be a potential target for the treatment of gastric carcinoma.

show abstract

Section: Journal Of Asian Natural Products Researchmentioning

confidence: 98%

Ras/ERK signaling pathway is involved in curcumin-induced cell cycle arrest and apoptosis in human gastric carcinoma AGS cells

Tang

Zhou

et al. 2014

Journal of Asian Natural Products Research

View full text Add to dashboard Cite

show abstract

“…137 However, nimbolide, azadirone, and g-yocotrienol induce DR expression through p53 expression that is mediated by an ERK-p53 mechanism(s). [121][122][123] Similarly, lupulone and damnacanthal (isolated from Morinda citrifolia) can upregulate DRs through induction of both p38-p53 mediated mechanism(s). 130,138 These studies indicate that p53 plays an important role in induction of DRs by natural compounds, which can significantly sensitize tumor cells to TRAIL therapy.…”

Section: Natural Compounds That Can Sensitize Tumor Cells To Trailmentioning

confidence: 99%

“…106,118-120 Azadirone (a limonoid tetranortriterpene), g-tocotrienol (an unsaturated vitamin E present predominantly in palm oil), and nimbolide (a terpenoid lactone derived from azadirachta indica) [121][122][123] induce DRs through activation of ERK1/2 mediated by activation of p53 pathways. Zerumbone (a component of Asian ginger) has been shown to upregulate DR expression through Tolcher et al 74 Hotte et al 75 Mom et al 76 Leong et al Note: TRAIL, tumor necrosis factor-related apoptosis-inducing ligand; n, number of patients enrolled; CR, complete response; PR, partial response; NA, data about responses (efficacy) were not reported; RCT, randomized-controlled trials.…”

Section: Natural Compounds That Can Sensitize Tumor Cells To Trailmentioning

confidence: 99%

Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy

Dai

Zhang

Arfuso

et al. 2015

Exp Biol Med (Maywood)

163

109

View full text Add to dashboard Cite

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to selectively induce apoptotic cell death in various tumor cells by engaging its death-inducing receptors (TRAIL-R1 and TRAIL-R2). This property has led to the development of a number of TRAIL-receptor agonists such as the soluble recombinant TRAIL and agonistic antibodies, which have shown promising anticancer activity in preclinical studies. However, besides activating caspase-dependent apoptosis in several cancer cells, TRAIL may also activate nonapoptotic signal transduction pathways such as nuclear factor-kappa B, mitogen-activated protein kinases, AKT, and signal transducers and activators of transcription 3, which may contribute to TRAIL resistance that is being now frequently encountered in various cancers. TRAIL resistance can be overcome by the application of efficient TRAILsensitizing pharmacological agents. Natural compounds have shown a great potential in sensitizing cells to TRAIL treatment through suppression of distinct survival pathways. In this review, we have summarized both apoptotic and nonapoptotic pathways activated by TRAIL, as well as recent advances in developing TRAIL-receptor agonists for cancer therapy. We also briefly discuss combination therapies that have shown great potential in overcoming TRAIL resistance in various tumors.

show abstract

“…Notably, 9 of the 18 genes were associated with neoplasms in their annotations. Examples include TNFRSF10B, inducing apoptosis in various solid tumors, [15][16][17][18][19] PTPN13 being upregulated in pancreatic cancer and Ewing sarcoma, 20,21 or IER3 and CCR4 that have a role in myelodysplastic syndromes and lymphoma, respectively. 22,23 In addition, TP63 contributes to tumorigenesis in several cancers.…”

mentioning

confidence: 99%

Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death

Beyer

Krönung

Leha³

et al. 2015

Cell Death Differ

View full text Add to dashboard Cite

The long terminal repeat (LTR) of human endogenous retrovirus type 9 (ERV9) acts as a germline-specific promoter that induces the expression of a proapoptotic isoform of the tumor suppressor homologue p63, GTAp63, in male germline cells. Testicular cancer cells silence this promoter, but inhibitors of histone deacetylases (HDACs) restore GTAp63 expression and give rise to apoptosis. We show here that numerous additional transcripts throughout the genome are driven by related ERV9-LTRs. 3' Rapid amplification of cDNA ends (3'RACE) was combined with next-generation sequencing to establish a large set of such mRNAs. HDAC inhibitors induce these ERV9-LTR-driven genes but not the LTRs from other ERVs. In particular, a transcript encoding the death receptor DR5 originates from an ERV9-LTR inserted upstream of the protein coding regions of the TNFRSF10B gene, and it shows an expression pattern similar to GTAp63. When treating testicular cancer cells with HDAC inhibitors as well as the death ligand TNF-related apoptosis-inducing ligand (TRAIL), rapid cell death was observed, which depended on TNFRSF10B expression. HDAC inhibitors also cooperate with cisplatin (cDDP) to promote apoptosis in testicular cancer cells. ERV9-LTRs not only drive a large set of human transcripts, but a subset of them acts in a proapoptotic manner. We propose that this avoids the survival of damaged germ cells. HDAC inhibition represents a strategy of restoring the expression of a class of ERV9-LTR-mediated genes in testicular cancer cells, thereby re-enabling tumor suppression.

show abstract

Azadirone, a Limonoid Tetranortriterpene, Induces Death Receptors and Sensitizes Human Cancer Cells to Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) through a p53 Protein-independent Mechanism

Cited by 57 publications

References 51 publications

Ras/ERK signaling pathway is involved in curcumin-induced cell cycle arrest and apoptosis in human gastric carcinoma AGS cells

Ras/ERK signaling pathway is involved in curcumin-induced cell cycle arrest and apoptosis in human gastric carcinoma AGS cells

Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy

Comprehensive identification of genes driven by ERV9-LTRs reveals TNFRSF10B as a re-activatable mediator of testicular cancer cell death

Contact Info

Product

Resources

About