Ilimaquinone induces death receptor expression and sensitizes human colon cancer cells to TRAIL-induced apoptosis through activation of ROS-ERK/p38 MAPK–CHOP signaling pathways

Truong, Minh; Na, MinKyun; Kim, Hyung Gyun; Khanal, Tilak; Choi, Jae Ho; Jin, Sun Woo; Oh, Seok Hoon; Hwang, In Hyun; Chung, Young Chul; Kim, Hee Suk; Jeong, Tae Cheon; Jeong, Hye Gwang

doi:10.1016/j.fct.2014.06.001

Cited by 48 publications

(40 citation statements)

References 37 publications

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“…Interestingly, although BIP or CHOP were induced after ER stress stimulation in all cell lines, and despite the fact that they likely contribute to both TRAIL-R1 and TRAIL-R2 up-regulation [10, 18] (Figure 5A), the percentage of cells undergoing apoptosis varied both depending on the cell line and the ER stress-inducer (Figure 5A). These finding suggest that UPR-mediated apoptosis may not be strictly correlated with transcriptional regulation of TRAIL-R1 and TRAIL-R2.…”

Section: Resultsmentioning

confidence: 99%

TRAIL receptor gene editing unveils TRAIL-R1 as a master player of apoptosis induced by TRAIL and ER stress

et al. 2016

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TRAIL induces selective tumor cell death through TRAIL-R1 and TRAIL-R2. Despite the fact that these receptors share high structural homologies, induction of apoptosis upon ER stress, cell autonomous motility and invasion have solely been described to occur through TRAIL-R2. Using the TALEN gene-editing approach, we show that TRAIL-R1 can also induce apoptosis during unresolved unfolded protein response (UPR). Likewise, TRAIL-R1 was found to co-immunoprecipitate with FADD and caspase-8 during ER stress. Its deficiency conferred resistance to apoptosis induced by thaspigargin, tunicamycin or brefeldin A. Our data also demonstrate that tumor cell motility and invasion-induced by TRAIL-R2 is not cell autonomous but induced in a TRAIL-dependant manner. TRAIL-R1, on the other hand, is unable to trigger cell migration owing to its inability to induce an increase in calcium flux. Importantly, all the isogenic cell lines generated in this study revealed that apoptosis induced TRAIL is preferentially induced by TRAIL-R1. Taken together, our results provide novel insights into the physiological functions of TRAIL-R1 and TRAIL-R2 and suggest that targeting TRAIL-R1 for anticancer therapy is likely to be more appropriate owing to its lack of pro-motile signaling capability.

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Section: Resultsmentioning

confidence: 99%

TRAIL receptor gene editing unveils TRAIL-R1 as a master player of apoptosis induced by TRAIL and ER stress

et al. 2016

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“…ERK pathways may induce apoptosis through promoting caspase-8 signaling and the activation, or potentiating the activation of death receptors by increasing the level of death ligands such as TNFα or FasL, or death receptors such as Fas, DR4 or DR5. For example, llimaquinone, an anti-cancer agent, was found to upregulate the expression of death receptor DR-4/-5 through ERK activation in colon cancer cell lines HCT116 and HT-29 [67]. …”

Section: Discussionmentioning

confidence: 99%

Dual roles of extracellular signal-regulated kinase (ERK) in quinoline compound BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer cells

Fong

Chang

et al. 2017

Cancer Cell Int

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Background2,9-Bis[2-(pyrrolidin-1-yl)ethoxy]-6-{4-[2-(pyrrolidin-1-yl)ethoxy] phenyl}-11H-indeno[1,2-c]quinoline-11-one (BPIQ), is a synthetic quinoline analog. A previous study showed the anti-cancer potential of BPIQ through modulating mitochondrial-mediated apoptosis. However, the effect of BPIQ on cell migration, an index of cancer metastasis, has not yet been examined. Furthermore, among signal pathways involved in stresses, the members of the mitogen-activated protein kinase (MAPK) family are crucial for regulating the survival and migration of cells. In this study, the aim was to explore further the role of MAPK members, including JNK, p38 and extracellular signal-regulated kinase (ERK) in BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer (NSCLC) cells.MethodsWestern Blot assay was performed for detecting the activation of MAPK members in NSCLC H1299 cells following BPIQ administration. Cellular proliferation was determined using a trypan blue exclusion assay. Cellular apoptosis was detected using flow cytometer-based Annexin V/propidium iodide dual staining. Cellular migration was determined using wound-healing assay and Boyden’s chamber assay. Zymography assay was performed for examining MMP-2 and -9 activities. The assessment of MAPK inhibition was performed for further validating the role of JNK, p38, and ERK in BPIQ-induced growth inhibition, apoptosis, and migration of NSCLC cells.ResultsWestern Blot assay showed that BPIQ treatment upregulates the phosphorylated levels of both MAPK proteins JNK and ERK. However, only ERK inhibitor rescues BPIQ-induced growth inhibition of NSCLC H1299 cells. The results of Annexin V assay further confirmed the pro-apoptotic role of ERK in BPIQ-induced cell death of H1299 cells. The results of wound healing and Boyden chamber assays showed that sub-IC50 (sub-lethal) concentrations of BPIQ cause a significant inhibition of migration in H1299 cells accompanied with downregulating the activity of MMP-2 and -9, the motility index of cancer cells. Inhibition of ERK significantly enhances BPIQ-induced anti-migration of H1299 cells.ConclusionsOur results suggest ERK may play dual roles in BPIQ-induced apoptosis and anti-migration, and it would be worthwhile further developing strategies for treating chemoresistant lung cancers through modulating ERK activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12935-017-0403-0) contains supplementary material, which is available to authorized users.

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“…It is now well known that CCAAT/enhancerbinding protein homologous protein (CHOP) is involved in regulation of DR4 and DR5 expression. In-vitro analysis also indicated that ERK and p38 MAPK signaling pathways were activated in Ilimaquinone treated colon cancer cells (Do et al, 2014).…”

Section: Ilimaquinonementioning

confidence: 94%

Drugs from Marine Sources: Modulation of TRAIL Induced Apoptosis in Cancer Cells

Farooqı

Attar²,

Gasparri³

2014

Asian Pacific Journal of Cancer Prevention

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There have been overwhelming advances in molecular oncology and data obtained through high-throughput technologies have started to shed light on wide ranging molecular mechanisms that underpin cancer progression. Increasingly it is being realized that marine micro-organisms and the biodiversity of plankton are rich sources of various anticancer compounds. Marine derived compounds play major roles in inducing apoptosis in cancer cells. More importantly, various agents have been noted to enhance TRAIL induced apoptosis in cancer cells by functionalizing intrinsic and extrinsic pathways. In this commentary, a list of marine derived compounds reported to induce apoptosis is discussed.

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Ilimaquinone induces death receptor expression and sensitizes human colon cancer cells to TRAIL-induced apoptosis through activation of ROS-ERK/p38 MAPK–CHOP signaling pathways

Cited by 48 publications

References 37 publications

TRAIL receptor gene editing unveils TRAIL-R1 as a master player of apoptosis induced by TRAIL and ER stress

TRAIL receptor gene editing unveils TRAIL-R1 as a master player of apoptosis induced by TRAIL and ER stress

Dual roles of extracellular signal-regulated kinase (ERK) in quinoline compound BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer cells

Drugs from Marine Sources: Modulation of TRAIL Induced Apoptosis in Cancer Cells

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