Endoplasmic reticulum stress, cell death and tumor: Association between endoplasmic reticulum stress and the apoptosis pathway in tumors (Review)

Fu, Xiaojing; Cui, Juanjuan; Meng, Xiangjun; Jiang, Piyu; Zheng, Qiuling; Zhao, Wenwen; Chen, Xuehong

doi:10.3892/or.2021.7933

Cited by 74 publications

(50 citation statements)

References 95 publications

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“…Endoplasmic reticulum stress (ER stress) occurs when proteins are not properly folded or conformed. Multiple studies have described the relation between ER stress and cancer [19,20]. Consistent with this concept, we extracted RNA from shikonin treated HCT-116 and HCT15, examined the expression level of the principal genes involved in endoplasmic reticulum (ER) stress by conducting RT_PCR.…”

Section: Shikonin Induced Endoplasmic Reticulum Stressmentioning

confidence: 81%

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Qi¹,

Zhang²,

Liu³

et al. 2022

J. Cancer

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Shikonin is a naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon, which has displayed potent anti-tumor properties. However, the effects of shikonin in colorectal cancer cells have not been yet fully investigated. In this study, we demonstrated that shikonin significantly inhibited the activity of colorectal cancer cells in a time-and dose-dependent manner. The flow cytometry and western blot results indicated that shikonin induced cell apoptosis by down-regulating BCL-2 and activating caspase-3/9 and the cleavage of PARP. The expression of BiP and the PERK/elF2α/ATF4/CHOP and IRE1α /JNK signaling pathways were upregulated after shikonin treatment. The pre-treatment with N-acetyl cysteine significantly reduced the cytotoxicity of shikonin. Taken together, shikonin could inhibit proliferation of the colorectal cancer cell through the activation of ROS mediated-ER stress. The in vivo results showed that shikonin effectively inhibited tumor growth in the HCT-116 and HCT-15 xenograft models. In conclusion, shikonin inhibited the proliferation of colorectal cancer cells in vitro and in vivo and warrants future investigation.

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Section: Shikonin Induced Endoplasmic Reticulum Stressmentioning

confidence: 81%

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Qi¹,

Zhang²,

Liu³

et al. 2022

J. Cancer

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“…Although UPR is mainly activated as an adaptive response to help cancer cells face stressful conditions [27], ER stress and UPR may be manipulated to induce cell death. This may represent a promising therapeutic option against MM and PEL, cancers characterized by a high level of basal stress that may be exacerbated to activate the pro-death functions of UPR [28]. Due to the constitutive ER stress, treatment with proteasome inhibitors such as Bortezomib, which may exacerbate it, also represent a therapeutic option against these cancers [21,29].…”

Section: Discussionmentioning

confidence: 99%

Targeting c-Myc Unbalances UPR towards Cell Death and Impairs DDR in Lymphoma and Multiple Myeloma Cells

et al. 2022

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Multiple myeloma (MM) and primary effusion lymphoma (PEL) are aggressive hematological cancers, for which the search for new and more effective therapies is needed. Both cancers overexpress c-Myc and are highly dependent on this proto-oncogene for their survival. Although c-Myc inhibition has been shown to reduce PEL and MM survival, the underlying mechanisms leading to such an effect are not completely clarified. In this study, by pharmacologic inhibition and silencing, we show that c-Myc stands at the cross-road between UPR and DDR. Indeed, it plays a key role in maintaining the pro-survival function of UPR, through the IRE1α/XBP1 axis, and sustains the expression level of DDR molecules such as RAD51 and BRCA1 in MM and PEL cells. Moreover, we found that c-Myc establishes an interplay with the IRE1α/XBP1 axis whose inhibition downregulated c-Myc, skewed UPR towards cell death and enhanced DNA damage. In conclusion, this study unveils new insights into the molecular mechanisms leading to the cytotoxic effects of c-Myc inhibition and reinforces the idea that its targeting may be a promising therapeutic approach against MM and PEL that, although different cancers, share some similarities, including c-Myc overexpression, constitutive ER stress and poor response to current chemotherapies.

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“…It is well documented that ER stress is triggered by the disruption of homeostasis in the ER and results in the activation of the unfolded protein response (UPR) ( Lu et al, 2014 ; Fu et al, 2021 ). When the unfolded or misfolded proteins in the ER accumulate and exceed a tolerable threshold, the function of ER may be lost and be difficult to restore leading to cellular dysfunction and apoptosis ( Gorman et al, 2012 ; Verfaillie et al, 2013 ; Hu et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Pitavastatin protects against neomycin-induced ototoxicity through inhibition of endoplasmic reticulum stress

Wang

Guan

et al. 2022

Front. Mol. Neurosci.

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Irreversible injury to inner ear hair cells induced by aminoglycoside antibiotics contributes to the formation of sensorineural hearing loss. Pitavastatin (PTV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been reported to exert neuroprotective effects. However, its role in aminoglycoside-induced hearing loss remains unknown. The objectives of this study were to investigate the beneficial effects, as well as the mechanism of action of PTV against neomycin-induced ototoxicity. We found that PTV remarkably reduced hair cell loss in mouse cochlear explants and promoted auditory HEI-OC1 cells survival after neomycin stimulation. We also observed that the auditory brainstem response threshold that was increased by neomycin was significantly reduced by pretreatment with PTV in mice. Furthermore, neomycin-induced endoplasmic reticulum stress in hair cells was attenuated by PTV treatment through inhibition of PERK/eIF2α/ATF4 signaling. Additionally, we found that PTV suppressed the RhoA/ROCK/JNK signal pathway, which was activated by neomycin stimulation in HEI-OC1 cells. Collectively, our results showed that PTV might serve as a promising therapeutic agent against aminoglycoside-induced ototoxicity.

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Endoplasmic reticulum stress, cell death and tumor: Association between endoplasmic reticulum stress and the apoptosis pathway in tumors (Review)

Cited by 74 publications

References 95 publications

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Shikonin induced Apoptosis Mediated by Endoplasmic Reticulum Stress in Colorectal Cancer Cells

Targeting c-Myc Unbalances UPR towards Cell Death and Impairs DDR in Lymphoma and Multiple Myeloma Cells

Pitavastatin protects against neomycin-induced ototoxicity through inhibition of endoplasmic reticulum stress

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