Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer

Zou, Peng; Chen, Minxiao; Ji, Jiansong; Chen, Weiqian; Chen, Xi; Ying, Shilong; Zhang, Junru; Zhang, Ziheng; Liu, Zhiguo; Yang, Shulin; Liang, Guang

doi:10.18632/oncotarget.5364

Cited by 115 publications

(103 citation statements)

References 38 publications

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“…It was determined that the appropriate inhibition of ERO1L may promote the transduction of an anti-severe ERS signal. Thus, ERO1L serves an important role in maintaining the function of ER and comprehensive abilities (10,31). In the present study, the expression of ERO1L in gastric cancer and adjacent normal tissue was determined by RT-qPCR and western blotting.…”

Section: Discussionmentioning

confidence: 84%

Expression of ERO1L in gastric cancer and its association with patient prognosis

Zhou

Wang

Gao

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to assess the expression of endoplasmic reticulum oxidoreductin-1-like (ERO1L) in gastric cancer and determine its association with patient prognosis. A total of 105 patients with gastric cancer undergoing radical gastrectomy were selected for the current study. Gastric cancer tissues (the observation group) and normal gastric tissue adjacent to the carcinoma (the control group) were resected from patients. Levels of ERO1L mRNA and protein in tumor tissues and adjacent tissues were detected using reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. Patients were divided into two groups: A positive group and negative group, according to the expression of ERO1. The expression of ERO1L in gastric cancer and its association with patient prognosis was analyzed. Levels of ERO1 mRNA and protein in gastric cancer were significantly higher than those of adjacent tissues (P<0.05). Immunohistochemical analysis demonstrated that there were 22 patients exhibiting negative expression of ERO1L and 83 patients exhibiting positive expression of ERO1L. The cumulative recurrence rates over 3 years in patients with positive expression of ERO1L were significantly higher than in patients with negative expression of ERO1L (P<0.05); the cumulative survival rates over 3 years in patients with positive expression of ERO1L were significantly lower than those of patients with negative expression of ERO1L (P<0.05). Thus, the current study determined that ERO1L was highly expressed in gastric cancer tissue. The high expression of ERO1L was associated with adverse prognoses in patients with gastric cancer. ERO1L may therefore be a therapeutic target for the prevention of gastric cancer.

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Section: Discussionmentioning

confidence: 84%

Expression of ERO1L in gastric cancer and its association with patient prognosis

Zhou

Wang

Gao

et al. 2017

Experimental and Therapeutic Medicine

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“…In our study, ROS generation was increased by LA in a dose-dependent manner, and blocking ROS production by NAC almost completely abrogated LA-induced apoptosis and dramatically attenuated LA-induced Bip, PERK and CHOP expression, indicating that ROS generation is an upstream event of ER stress induced by LA. The interplay between ROS and ER stress is controversial; ROS can either trigger the activation of ER stress or can be a consequence of ER stress [9, 12-15]. We found that NAC was able to inhibit ROS production (Fig.…”

Section: Discussionmentioning

confidence: 90%

“…Recently, studies showed that ER stress can be activated as a downstream event of oxidative stress-mediated apoptosis, and in several instances, both of these processes can occur together [9-11]. To investigate the role of ER stress in LA-induced apoptosis, the expression of ER stress-related proteins, including Bip, p-eIF2α, and CHOP was measured by western blot analysis.…”

Section: Resultsmentioning

confidence: 99%

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Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells

Yang¹,

Zhang²,

Wang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Levistolide A (LA), a natural compound isolated from the traditional Chinese herb Ligusticum chuanxiong Hort, is used for treating cancer. In this study, we investigated the anticancer effect of LA in HCT116 and its isogenic p53-/- colon cancer cells, as well as the underlying mechanisms. Methods: MTT assay was used to evaluate the effect of LA on the viability of cancer cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined by flow cytometry. Protein expression was detected by western blotting. Results: The results showed that LA inhibited viability and caused apoptosis of both wild-type and p53-/- HCT116 cells. LA was able to trigger production of ROS and endoplasmic reticulum (ER) stress. Inhibition of ROS using N-acetylcysteine abrogated LA-induced ER stress and apoptosis, as well as the reduction in cancer cell viability. Conclusion: Our results indicate that LA causes apoptosis of colon cancer cells via ROS-mediated ER stress pathway. It will be interesting to develop the natural compound for chemotherapy of cancers such as CRC.

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“…Furthermore, studies have shown that ROS production in cancer cells is one of the mechanisms underlying the synergetic cytotoxicity observed in cases of combination anti-tumor treatments [43,44]. Therefore, we determined whether ROS generation plays a role in the combined cytotoxic effects of Rp and ω-3 PUFAs.…”

Section: Zhu Et Al: ω-3 Pufas and Rapamycin Co-treatment Induces Synmentioning

confidence: 96%

Metabolic Shift Induced by ω -3 PUFAs and Rapamycin Lead to Cancer Cell Death

Zhu

Feng

Lin

et al. 2018

Cell Physiol Biochem

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Background/Aims: Rapamycin (Rp), the main mammalian target of rapamycin complex inhibitor, is a promising therapeutic agent for breast cancer. However, metabolic disorders and drug resistance reduce its efficacy. Epidemiological, clinical, and experimental studies have demonstrated that omega-3 polyunsaturated fatty acids (ω-3 PUFAs) significantly reduce the incidence and mortality of breast cancer and improve metabolic disorders. Methods: Three breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Rp plus ω-3 PUFA treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics, seahorse experiments, and western blot analysis. Results: We found that ω-3 PUFAs and Rp synergistically induced cell cycle arrest and apoptosis in vitro and in vivo, accompanied by autophagy blockage. In addition, Rp-induced hypertriglyceridemia and hypercholesterolemia were completely abolished by ω-3 PUFA supplementation. Moreover, the combined treatment of ω-3 PUFA and Rp significantly inhibited glycolysis and glutamine metabolism. The anti-tumor effects of this combination treatment were dependent on ROS production, which was increased by β-oxidation and oxidative phosphorylation. Conclusion: Our study revealed that ω-3 PUFA enhanced the anti-tumor activity of Rp while minimizing its side effects in vitro and in vivo. These results provide novel insights into the mechanisms underlying the potential beneficial effects of Rp combined with ω-3 PUFAs on the prevention of breast cancer.

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Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer

Cited by 115 publications

References 38 publications

Expression of ERO1L in gastric cancer and its association with patient prognosis

Expression of ERO1L in gastric cancer and its association with patient prognosis

Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells

Metabolic Shift Induced by ω -3 PUFAs and Rapamycin Lead to Cancer Cell Death

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