Propofol prevents oxidative stress and apoptosis by regulating iron homeostasis and targeting JAK/STAT3 signaling in SH-SY5Y cells

Zhang, Ying; Zuo, Yong; Li, Bowen; Jinhong, Xie; Ma, Zhao; Thirupathi, Anand; Yu, Peng; Gao, Guofen; Shi, Mengtong; Zhou, Changle; Xu, Hongmeng; Chang, Yan‐Zhong; Shi, Zhenhua

doi:10.1016/j.brainresbull.2019.08.018

Cited by 27 publications

(21 citation statements)

References 29 publications

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“…To examine the ferrous chelating ability of nuciferine, the levels in the medium (containing nuciferine, deferoxamine, ferric ammonium citrate, deferoxamine plus ferric ammonium citrate, and nuciferine plus ferric ammonium citrate, respectively) were monitored by measuring the formation of the ferrous ion ferrozine complexes (Zhang et al, 2019). The reaction mixture contained cell culture medium (0.2 ml, no cells), ferrozine (0.1 ml), and a mixed liquor of glycine (2 ml, 100 mM) and hydroxylamine hydrochloride (2 mM) to initiate the reaction, and the mixture was shaken vigorously for 15 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis

Liu

Fan

et al. 2021

British J Pharmacology

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103

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Background and Purpose Acute kidney injury is a common clinical problem with no definitive or specific treatment. Therefore, the molecular mechanisms of acute kidney injury must be fully understood to develop novel treatments. Nuciferine, a major bioactive compound isolated from the lotus leaf, possesses extensive pharmacological activities. Its effect on folic acid‐induced acute kidney injury, however, remains unknown. Here, we aimed to clarify the pharmacological effects of nuciferine and its mechanisms of action in acute kidney injury. Experimental Approach The effects of nuciferine on folic acid‐induced acute kidney injury in mice were investigated. HK‐2 human proximal tubular epithelial cells and HEK293T HEK cells were used to evaluate the protective effect of nuciferine on RSL3‐induced ferroptosis. Key Results Nuciferine treatment mitigated the pathological alterations, ameliorated inflammatory cell infiltration and improved kidney dysfunction in mice with folic acid‐induced acute kidney injury. In HK‐2 and HEK293T cells, nuciferine significantly prevented RSL3‐induced ferroptotic cell death. Mechanistically, nuciferine significantly inhibited ferroptosis by preventing iron accumulation and lipid peroxidation in vitro and in vivo. Moreover, knockdown of glutathione (GSH) peroxidase 4 (GPX4) abolished the protective effect of nuciferine against ferroptosis. Conclusion and Implications Nuciferine ameliorated renal injury in mice with acute kidney injury, perhaps by inhibiting the ferroptosis. Nuciferine may represent a novel treatment that improves recovery from acute kidney injury by targeting ferroptosis.

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Section: Methodsmentioning

confidence: 99%

Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis

Liu

Fan

et al. 2021

British J Pharmacology

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103

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“…For example, propofol was found to enhance cisplatin-induced cell apoptosis in cervical cancer cells via the EGFR/JAK2/STAT3 signaling pathway ( 35 ). Propofol also prevented oxidative stress and apoptosis by regulating iron homeostasis and targeting the JAK/STAT3 signaling pathway in SH-SY5Y cells ( 36 ). In addition, a previous study demonstrated that propofol inhibited cell invasion and promoted cell apoptosis by regulating the STAT3/HOX transcript antisense RNA axis in CRC ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression

Zhao

Chen

2021

Oncol Lett

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Propofol is a commonly used intravenous anesthetic agent that can also suppress the proliferation of various human cancer types, including colorectal cancer (CRC). The present study aimed to investigate whether propofol could induce the ferroptosis of CRC cells by regulating signal transducer and activator of transcription 3 (STAT3). STAT3 expression in normal and CRC tissues was measured. Human normal colonic epithelial NCM460 cells and human CRC SW480 cells were exposed to different concentrations of propofol and then cell viability was detected. SW480 cells were transfected with a vector overexpressing STAT3 and treated with propofol, and the cell viability, colony formation, cell proliferation, iron level, ROS production and ferroptosis of these cells and control cells were evaluated. Overall, the results showed that STAT3 was highly expressed in CRC tissues. Propofol exerted no marked effect on NCM460 cell viability, but inhibited SW480 cell viability in a concentration-dependent manner. Meanwhile, STAT3 was downregulated by propofol in a concentration-dependent manner. Propofol also inhibited CRC cell proliferation and colony formation, and enhanced cellular iron and ROS levels. Additionally, the expression of proteins involved in ferroptosis was also altered by propofol, including the upregulation of CHAC1 and PTGS2 expression in CRC cells, and the inhibition of GPX4 expression. However, STAT3 overexpression blocked the effect of propofol on CRC cells. In conclusion, propofol may trigger the ferroptosis of CRC cells by downregulating STAT3 expression.

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“…The reduced cell numbers and prolonged doubling times in the presence of cystatin C could be due to either a decreased proliferation rate or increased cell death. Analysis of cell death by measuring cell area and optical thickness by phase holographic microscopy has been conducted previously for TUNEL positive neuroblastoma cells [28]. To address the possibility that cystatin C is inducing cell death, we studied the morphology of cells cultured with or without cystatin C in phase hologram images.…”

Section: Resultsmentioning

confidence: 99%

“…A scatter plot of cell area (µm), and average optical thickness (µm) was made at time-points 0, 12 and 24 hours using all cells from all wells and positions of each treatment. Phase holograms have earlier been used to study altered thickness and area, which are known properties of dead cells [28].…”

Section: Analysis Of Cell Morphologymentioning

confidence: 99%

Externally added cystatin C reduces growth of A375 melanoma cells by increasing cell cycle time

2021

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Some secreted cysteine protease inhibitors of the cystatin family appear to affect intracellular proteolysis and growth of human cells, as a result of internalization. Here, we studied the effects of external addition of the most abundant human cystatin, cystatin C, on viability and proliferation of cancer cells in culture. A dose-dependent decrease of viable cells was seen for A375 melanoma, MCF-7 breast cancer and PC-3 prostate cancer cells cultured in 1-5 M cystatin C after 24 h.Real-time assessment of growth rates in A375 cell cultures for 48 h by digital holographic microscopy showed an increased doubling time for cells cultured in the presence of 5 M cystatin C (20.1 h) compared to control cells (14.7 h). A prolonged doubling time was already observed during the first 12 h, indicating a rapid general decrease of cell proliferation at the population level. Tracking of individual cells in phase holographic images showed that dividing cells incubated with 5 µM cystatin C underwent fewer mitoses during 48 h than control cells. In addition, the time between cell divisions was longer, especially for the first cell cycle. Incubation with the variant W106F-cystatin C (with high cellular uptake rate) resulted in a lower number of viable cells and a prolonged doubling time than when cells were incubated with wild-type cystatin C, but no effect was observed for (R24A,R25A)-cystatin C (low cellular uptake). Thus, cystatin C causes prolonged cell division leading to decreased proliferation of melanoma cells, and internalization seems to be a prerequisite for this effect.

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Propofol prevents oxidative stress and apoptosis by regulating iron homeostasis and targeting JAK/STAT3 signaling in SH-SY5Y cells

Cited by 27 publications

References 29 publications

Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis

Nuciferine protects against folic acid‐induced acute kidney injury by inhibiting ferroptosis

Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression

Externally added cystatin C reduces growth of A375 melanoma cells by increasing cell cycle time

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