Imiquimod induces ER stress and Ca 2+ influx independently of TLR7 and TLR8

Nyberg, William A.; Espinosa, Alexander

doi:10.1016/j.bbrc.2016.03.080

Cited by 19 publications

(22 citation statements)

References 28 publications

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“…5). Recent evidence has shown that IMQ can still induce ER stress in mouse Tlr7 À/À cells [33]. Thus, in agreement with the above-mentioned report, our results demonstrate that IMQ induced ER stress independently of TLR7 and TLR8.…”

Section: Discussionsupporting

confidence: 93%

Imiquimod-induced autophagy is regulated by ER stress-mediated PKR activation in cancer cells

Chang

Huang

Wang

et al. 2017

Journal of Dermatological Science

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Section: Discussionsupporting

confidence: 93%

Imiquimod-induced autophagy is regulated by ER stress-mediated PKR activation in cancer cells

Chang

Huang

Wang

et al. 2017

Journal of Dermatological Science

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“…Although imiquimod is an agonist of TLR7, previous studies have shown that it can exert effects in tumour cells via TLR7-independent mechanisms [13, 18, 37, 38]. To determine whether this is the case in DFTD, we examined TLR7 expression in DFT1 and DFT2 cell lines.…”

Section: Resultsmentioning

confidence: 99%

The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines

et al. 2016

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The survival of the Tasmanian devil (Sarcophilus harrisii) is threatened by devil facial tumour disease (DFTD). This transmissible cancer is usually fatal, and no successful treatments have been developed. In human studies, the small immunomodulatory molecule imiquimod is a successful immunotherapy, activating anti-tumour immunity via stimulation of toll-like receptor-7 (TLR7) signaling pathways. In addition, imiquimod is a potent inducer of apoptosis in human tumour cell lines via TLR7 independent mechanisms. Here we investigate the potential of imiquimod as a DFTD therapy through analysis of treated DFTD cell lines and Tasmanian devil fibroblasts. WST-8 proliferation assays and annexin V apoptosis assays were performed to monitor apoptosis, and changes to the expression of pro- and anti-apoptotic genes were analysed using qRT-PCR. Our results show that DFTD cell lines, but not Tasmanian devil fibroblasts, are sensitive to imiquimod-induced apoptosis in a time and concentration dependent manner. Induction of apoptosis was accompanied by down-regulation of the anti-apoptotic BCL2 and BCLXL genes, and up-regulation of the pro-apoptotic BIM gene. Continuous imiquimod treatment was required for these effects to occur. These results demonstrate that imiquimod can deregulate DFTD cell growth and survival in direct and targeted manner. In vivo, this may increase DFTD vulnerability to imiquimod-induced TLR7-mediated immune responses. Our findings have improved the current knowledge of imiquimod action in tumour cells for application to both DFTD and human cancer therapy.

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“…Prostate cancer cells (PC3) were cultured in Roswell Park Memorial Institute (RPMI)-1640 medium with 10% fetal bovine serum (FBS) and 1% of 100 unit/mL of penicillin and streptomycin,20 and normal prostate cells (RWPE-1) were cultured in a concentration of 4×10 4 keratinocyte serum-free medium (K-SFM) supplemented with 0.2 ng/mL human epidermal growth factor (rhEGF) and 25 µg/mL bovine pituitary extract (BPE)21 and 1× antibiotic/antimycotic solution. Cultures were incubated at 37°C in a humidified atmosphere containing 5% CO 2 and passed weekly 22–24…”

Section: Methodsmentioning

confidence: 99%

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

Babaei

Huri

Kamalıdehghan

et al. 2017

OTT

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Litsea is considered as an evergreen genus distributed in tropical and subtropical Asia; this genus belongs to the large family of Lauraceae. In this study, the cell-death metabolism of biseugenol B was investigated. Nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and release of cytochrome c have been detected in human prostate cancer cell line (PC3) treated with biseugenol B by high content screening (HCS). Fluorescent analysis was conducted to examine the reactive oxygen species formation. To determine the mechanism of cell death, the levels of Bcl-cell lymphoma (Bcl)-2 proteins, Bcl-2-associated X (Bax) protein and anti-apoptosis heat-shock protein 70 were tested by applying reverse transcription polymerase chain reaction and Western blot. Bioluminescent assays were also performed to assess the level of caspases such as 3/7, 8 and 9 during treatment. Furthermore, the involvement of nuclear factor kappa-B (NF-κB) was examined by Western blot and HCS. Biseugenol B showed significant cytotoxicity toward PC3 with no toxicity toward normal prostate cells (RWPE-1), which indicates that biseugenol B has qualities that induce apoptosis in tumor cells. The treatment of PC3 cells with biseugenol B provoked apoptosis with cell-death-transducing signals. Downregulation of Bcl-2 and upregulation of Bax regulated the MMP, which in turn caused the release of cytochrome c from mitochondria into cytosol. The release of cytochrome c activated caspase-9, which consequently activated caspase-3/7 with the cleaved poly(ADP-ribose) polymerase protein, thereby resulting in apoptosis alteration. Involvement of an extrinsic apoptosis pathway was exhibited by the increase in caspase-8, while the increase in caspase-3/7 and caspase-9 demonstrated involvement of an intrinsic apoptosis pathway. Meanwhile, no significant increase was observed in caspases 3/7, 8 or 9 in normal prostate cells (RWPE-1) after treatment with biseugenol B. Prevention of NF-κB translocation from the cytosol to the nucleus occurred in PC3 after treatment with biseugenol B. The results of our study reveal that biseugenol B triggers the apoptosis of PC3 cells via intrinsic and extrinsic apoptosis pathways and inhibition of NF-κB signaling pathway. Our findings suggest that biseugenol B is a potentially useful agent for prostate cancer treatment.

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Imiquimod induces ER stress and Ca 2+ influx independently of TLR7 and TLR8

Cited by 19 publications

References 28 publications

Imiquimod-induced autophagy is regulated by ER stress-mediated PKR activation in cancer cells

Imiquimod-induced autophagy is regulated by ER stress-mediated PKR activation in cancer cells

The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

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Imiquimod induces ER stress and Ca 2+ influx independently of TLR7 and TLR8

Cited by 19 publications

References 28 publications

Imiquimod-induced autophagy is regulated by ER stress-mediated PKR activation in cancer cells

Imiquimod-induced autophagy is regulated by ER stress-mediated PKR activation in cancer cells

The Immunomodulatory Small Molecule Imiquimod Induces Apoptosis in Devil Facial Tumour Cell Lines

Apoptotic induction and inhibition of NF-&kappa;B signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2&#39;-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study

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Product

Resources

About

Apoptotic induction and inhibition of NF-κB signaling pathway in human prostatic cancer PC3 cells by natural compound 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B, from <em>Litsea costalis</em>: an in vitro study