Proteasome Inhibitor PS-341 Induces Apoptosis through Induction of Endoplasmic Reticulum Stress-Reactive Oxygen Species in Head and Neck Squamous Cell Carcinoma Cells

Fribley, Andrew M.; Zeng, Qinghua; Wang, Cun Yu

doi:10.1128/mcb.24.22.9695-9704.2004

Cited by 380 publications

(389 citation statements)

References 48 publications

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“…20 What is more, proteasomal inhibitors can actually cause ER stress, as shown by the upregulation of Grp78/Bip and CHOP/GADD153, thus providing further evidence that proteasomal activity is intimately coupled to ERAD as the last leg of the UPR. 21,22 Recently, a potent proteasome inhibitor, PS-341 (Bortezomib), was shown to be effective in the treatment of multiple myeloma, and is now approved by the US Food and Drug Administration. The toxicity of PS-341 in multiple myeloma cells is very likely to be the result of ER stress-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic reticulum stress-induced cell death mediated by the proteasome

et al. 2007

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Section: Discussionmentioning

confidence: 99%

Endoplasmic reticulum stress-induced cell death mediated by the proteasome

et al. 2007

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“…The mitochondrial apoptotic pathway has been shown to play a role in proteasome inhibitor-induced apoptosis in several tumor cell models [13][14][15][16][17][18][19]. Therefore, we evaluated mitochondria integrity in DC exposed to bortezomib.…”

Section: Mitochondrial Damage In Response To Bortezomib In DCmentioning

confidence: 99%

“…How proteasome inhibition translates into a potent cytotoxic effect in tumor cells is not fully understood, even though inhibition of NF-jB and deregulated expression of p53, caspases, Bcl-2 family members, CDC25 family proteins and cyclins were all proposed to be relevant in this context [1,2]. Ultimately, deregulated protein turnover by proteasome inhibition leads to activation of the intrinsic apoptotic pathway as shown by mitochondria dysfunction, production of reactive oxygen species, and endoplasmic reticulum stress, which have all been observed in response to these drugs [13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Proteasome inhibitor‐induced apoptosis in human monocyte‐derived dendritic cells

et al. 2006

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Proteasome inhibitors possess potent antitumor activity against a broad spectrum of human malignancies. However, the effects of these compounds on the immune system still have to be clearly determined. In the present study, we have investigated the effects of proteasome inhibitors on dendritic cells (DC), antigen‐presenting cells playing a key role in the initiation of immune responses. Exposure to the proteasome inhibitors bortezomib, MG132 or epoxomicin was found to promote apoptosis of human monocyte‐derived DC and to reduce the yield of viable DC when given to monocytes early during differentiation to DC. DC apoptosis via proteasome inhibition was accompanied by mitochondria disruption and subsequent activation of the caspase cascade. Up‐regulation and intracellular redistribution of Bcl‐2‐associated X protein (Bax), a pro‐apoptotic Bcl‐2 family protein, were observed in DC treated with these compounds and represent a suitable mechanism leading to activation of the intrinsic apoptotic pathway. Finally, active protein synthesis was found to represent an upstream prerequisite for DC apoptosis induced by proteasome inhibitors, since the translation inhibitor cycloheximide blocked all of the steps of the observed apoptotic response. In conclusion, induction of apoptosis in DC may represent a novel mechanism by which proteasome inhibitors affect the immune response at the antigen‐presenting cell level.

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“…2003; Fribley et al. 2004; Holkova and Grant 2012). The most frequent adverse events with this drug are GI symptoms, peripheral neuropathy, fatigue, and thrombocytopenia (Holkova and Grant 2012; Argyriou et al.…”

Section: Introductionmentioning

confidence: 99%

Role of endoplasmic reticulum stress in drug‐induced toxicity

Foufelle

Fromenty

2016

Pharmacology Res & Perspec

194

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Drug‐induced toxicity is a key issue for public health because some side effects can be severe and life‐threatening. These adverse effects can also be a major concern for the pharmaceutical companies since significant toxicity can lead to the interruption of clinical trials, or the withdrawal of the incriminated drugs from the market. Recent studies suggested that endoplasmic reticulum (ER) stress could be an important event involved in drug liability, in addition to other key mechanisms such as mitochondrial dysfunction and oxidative stress. Indeed, drug‐induced ER stress could lead to several deleterious effects within cells and tissues including accumulation of lipids, cell death, cytolysis, and inflammation. After recalling important information regarding drug‐induced adverse reactions and ER stress in diverse pathophysiological situations, this review summarizes the main data pertaining to drug‐induced ER stress and its potential involvement in different adverse effects. Drugs presented in this review are for instance acetaminophen (APAP), arsenic trioxide and other anticancer drugs, diclofenac, and different antiretroviral compounds. We also included data on tunicamycin (an antibiotic not used in human medicine because of its toxicity) and thapsigargin (a toxic compound of the Mediterranean plant Thapsia garganica) since both molecules are commonly used as prototypical toxins to induce ER stress in cellular and animal models.

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Proteasome Inhibitor PS-341 Induces Apoptosis through Induction of Endoplasmic Reticulum Stress-Reactive Oxygen Species in Head and Neck Squamous Cell Carcinoma Cells

Cited by 380 publications

References 48 publications

Endoplasmic reticulum stress-induced cell death mediated by the proteasome

Endoplasmic reticulum stress-induced cell death mediated by the proteasome

Proteasome inhibitor‐induced apoptosis in human monocyte‐derived dendritic cells

Role of endoplasmic reticulum stress in drug‐induced toxicity

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