Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells

Yang, Yang; Jiang, Liping; She, Yan; Chen, Min; Li, Qiujuan; Yang, Guang; Chen, Geng; Tang, Liyun; Zhong, Laifu; Jiang, Lijie; Liu, Xiaofang

doi:10.1016/j.etap.2015.09.008

Cited by 26 publications

(13 citation statements)

References 29 publications

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“…Our results revealed that olaquindox treatment of HEK293 cells caused cytotoxicity and the corresponding IC 50 value was approximately 800 μg/mL ( Figure 1 A), which was consistent with the previous studies [ 23 ]. The IC 50 of HEK293 cells is similar to that of HepG2 cells treated with olaquindox [ 3 ].…”

Section: Discussionsupporting

confidence: 93%

TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells

Zhao

Yang

et al. 2017

Molecules

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Olaquindox, a feed additive, has drawn public attention due to its potential mutagenicity, genotoxicity, hepatoxicity and nephrotoxicity. The purpose of this study was to investigate the role of tuberous sclerosis complex (TSC2) pathways in olaquindox-induced autophagy in human embryonic kidney 293 (HEK293) cells. The results revealed that olaquindox treatment reduced the cell viability of HEK293 cells and downregulated the expression of TSC2 in a dose- and time-dependent manner. Meanwhile, olaquindox treatment markedly induced the production of reactive oxygen species (ROS), cascaded to autophagy, oxidative stress, and apoptotic cell death, which was effectively eliminated by the antioxidant N-acetylcysteine (NAC). Furthermore, overexpression of TSC2 attenuated olaquindox-induced autophagy in contrast to inducing the production of ROS, oxidative stress and apoptosis. Consistently, knockdown of TSC2 upregulated autophagy, and decreased olaquindox-induced cell apoptosis. In conclusion, our findings indicate that TSC2 partly participates in olaquindox-induced autophagy, oxidative stress and apoptosis, and demonstrate that TSC2 has a negative regulation role in olaquindox-induced autophagy in HEK293 cells.

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Section: Discussionsupporting

confidence: 93%

TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells

Zhao

Yang

et al. 2017

Molecules

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“…The p53 tumor suppressor gene serves important roles in the regulation of cell proliferation and apoptosis (10)(11)(12). p53 is activated by a number of intracellular and extracellular stressors, including irradiation, DNA damaging agents or reactive oxygen species (ROS) (13)(14)(15). Deficiencies in the function of p53 are critical events during the development of tumors and resistance to anticancer therapies (16,17).…”

Section: Introductionmentioning

confidence: 99%

Sulforaphane induces p53-deficient SW480 cell apoptosis via the ROS-MAPK signaling pathway

Lan

Yuan

Cai

2017

Molecular Medicine Reports

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Sulforaphane (SFN) has been revealed to inhibit the growth and induce apoptosis of cancer cells. However, the detailed anticancer effects of SFN on p53‑deficient colon cancer cells has yet to be clearly elucidated. The present study employed p53‑deficient SW480 cells to establish an SFN‑induced in vitro model of apoptosis. The critical events leading to apoptosis were then evaluated in SFN‑treated p53‑deficient SW480 cells, by performing an MTT assay, flow cytometry, western blotting and ELISA. The results demonstrated that SFN at concentrations of 5, 10, 15 and 20 µM induced mitochondria‑associated cell apoptosis, which was further confirmed by disruption of the mitochondrial membrane potential, an increase in the Bax/Bcl‑2 ratio, as well as activation of caspase‑3, ‑7 and ‑9. In addition, SFN‑induced apoptosis was associated with an increase in the generation of reactive oxygen species (ROS), and the activation of extracellular signal‑regulated kinases (Erk) and p38 mitogen‑activated protein kinases. However, SFN did not induce expression of the p53 family member, p73. SFN‑induced apoptosis was subsequently confirmed to be ROS‑dependent and associated with Erk/p38, as the specific inhibitors for ROS, phosphorylated (p)‑Erk and p‑p38, completely or partially attenuated the SFN‑induced reduction in SW480 cell viability. In addition, the results demonstrated that even at the lowest concentrations (5 µM), SFN increased the sensitivity of p53‑proficient HCT‑116 cells to cisplatin. In conclusion, the results suggest that SFN may induce apoptosis in p53‑deficient SW480 cells via p53/p73‑independent and ROS‑Erk/p38‑dependent signaling pathways.

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“…The assay was performed according to the manufacturer's protocol with slight modifications as reported previously. 24,25 L02 liver cells (1×10 6 /mL) were spread into a 6-well plate and allowed to grow for 48 hours. Subsequently, the cells were treated for 24 hours with QDs-1, QDs-2, and QDs-3 at 40 μmol/L Cd 2+ concentration, respectively.…”

Section: Comet Assaymentioning

confidence: 99%

Parallel comparative studies on toxicity of quantum dots synthesized and surface engineered with different methods in vitro and in vivo

Liu¹,

Ye²,

Wang³

et al. 2017

IJN

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Quantum dots (QDs) have been considered to be promising probes for biosensing, bioimaging, and diagnosis. However, their toxicity issues caused by heavy metals in QDs remain to be addressed, in particular for their in vivo biomedical applications. In this study, a parallel comparative investigation in vitro and in vivo is presented to disclose the impact of synthetic methods and their following surface modifications on the toxicity of QDs. Cellular assays after exposure to QDs were conducted including cell viability assessment, DNA breakage study in a single cellular level, intracellular reactive oxygen species (ROS) receptor measurement, and transmission electron microscopy to evaluate their toxicity in vitro. Mice experiments after QD administration, including analysis of hemobiological indices, pharmacokinetics, histological examination, and body weight, were further carried out to evaluate their systematic toxicity in vivo. Results show that QDs fabricated by the thermal decomposition approach in organic phase and encapsulated by an amphiphilic polymer (denoted as QDs-1) present the least toxicity in acute damage, compared with those of QDs surface engineered by glutathione-mediated ligand exchange (denoted as QDs-2), and the ones prepared by coprecipitation approach in aqueous phase with mercaptopropionic acid capped (denoted as QDs-3). With the extension of the investigation time of mice respectively injected with QDs, we found that the damage caused by QDs to the organs can be gradually recovered. This parallel comparative investigation suggests that synthetic methods and their resulting surface microenvironment play vital roles in the acute toxicity profiles of QDs. The present study provides updated insights into the fabrication and surface engineering of QDs for their translational applications in theranostics.

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Olaquindox induces DNA damage via the lysosomal and mitochondrial pathway involving ROS production and p53 activation in HEK293 cells

Cited by 26 publications

References 29 publications

TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells

TCS2 Increases Olaquindox-Induced Apoptosis by Upregulation of ROS Production and Downregulation of Autophagy in HEK293 Cells

Sulforaphane induces p53-deficient SW480 cell apoptosis via the ROS-MAPK signaling pathway

Parallel comparative studies on toxicity of quantum dots synthesized and surface engineered with different methods in vitro and in vivo

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