Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway

Ma, Yuyang; Di, Zemin; Cao, Qing; Xu, Wen-shuang; Bi, Sixing; Yu, Jishuang; Shen, Yujun; Yan, Yu; Feng, Lijie

doi:10.1038/s41401-019-0318-5

Cited by 40 publications

(31 citation statements)

References 40 publications

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“…CHOP is an important transcription factor involved in regulating apoptosis and drug sensitivity [168][169][170]. Studies have shown that the levels of CHOP mRNA and its protein level were significantly lower in lung cancer tissues compared with noncancerous tissues.…”

Section: Therapeutic Strategies Based On Ncrnas and The Upr In Cancermentioning

confidence: 99%

Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer

Zhao

Zeng

2020

J Hematol Oncol

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To survive, cancer cells are subjected to various internal and external adverse factors, including genetic mutations, hypoxia, nutritional deficiencies, and drug toxicity. All of these factors result in the accumulation of unfolded proteins in the endoplasmic reticulum, which leads to a condition termed endoplasmic reticulum stress (ER stress) and triggers the unfolded protein response (UPR). UPR downstream components strictly control transcription and translation reprogramming to ensure selective gene expression, including that of non-coding RNA (ncRNAs), to adapt to adverse environments. NcRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play important roles in regulating target gene expression and protein translation, and their aberrant expression is related to tumor development. Dysregulation of ncRNAs is involved in the regulation of various cellular characteristics of cancer cells, including growth, apoptosis, metastasis, angiogenesis, drug sensitivity, and tumor stem cell properties. Notably, ncRNAs and ER stress can regulate each other and collaborate to determine the fate of tumor cells. Therefore, investigating the interaction between ER stress and ncRNAs is crucial for developing effective cancer treatment and prevention strategies. In this review, we summarize the ER stress-triggered UPR signaling pathways involved in carcinogenesis followed by the mutual regulation of ER stress and ncRNAs in cancer, which provide further insights into the understanding of tumorigenesis and therapeutic strategies.

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Section: Therapeutic Strategies Based On Ncrnas and The Upr In Cancermentioning

confidence: 99%

Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer

Zhao

Zeng

2020

J Hematol Oncol

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“…For the detection of ER stress, the ER stress inhibitor 4-phenylbutyric acid (4-PBA; Sigma-Aldrich; Merck KGaA) at a concentration of 7 mM was used to pretreat AGS cells for 4 h at 37˚C, according to a previous study (9), to determine the role of SchA in ER stress.…”

Section: Methodsmentioning

confidence: 99%

Schizandrin A induces the apoptosis and suppresses the proliferation, invasion and migration of gastric cancer cells by activating endoplasmic reticulum stress

Qian

Wang³

et al. 2021

Mol Med Rep

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Apart from its basic antioxidant and anti-inflammatory properties, schizandrin A (SchA), which is isolated from Fructus schisandra, can exert anticancer effects on multiple cancer types. However, to the best of our knowledge, there has been no study identifying the impacts of SchA on gastric cancer (GC). Therefore, the aim of the present study was to identify how SchA functioned to affect the progression of GC. To investigate the role of SchA in GC development, Cell Counting Kit-8, colony formation, wound healing and Transwell assays were conducted to assess the viability, proliferation, migration and invasion of AGS cells, respectively. Then, the apoptosis rate and apoptosis-and endoplasmic reticulum (ER) stress-related protein expression levels in AGS cells exposed to SchA were detected via TUNEL assays and western blotting, respectively. Subsequently, the aforementioned functional assays were performed again in AGS cells exposed to both SchA and the ER stress inhibitor 4-phenylbutyric acid (4-PBA) for the confirmation of the effect of SchA on ER stress in GC. It was found that SchA markedly decreased the viability, proliferation, migration and invasion, while it induced the apoptosis of AGS cells. Moreover, the markers of ER stress were elevated by SchA treatment in AGS cells. Nevertheless, 4-PBA reversed the effects of SchA on the viability, proliferation, migration, invasion and apoptosis of AGS cells, accompanied by decreased expression of ER stress markers. In conclusion, the present study demonstrated that SchA induced the apoptosis and suppressed the proliferation, invasion and migration of GC cells by activating ER stress, which provides a theoretical basis for the use of SchA in the treatment of GC.

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“…Briefly, after treatment with the test compounds for 18 h, A549 cells were collected and lysed with ice-cold RIPA lysis buffer containing proteinase inhibitors. The expression of TrxR proteins after treatment with the test compounds was analyzed by Western blot as previously described [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation

Sun

et al. 2021

Molecules

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Chemotherapeutic agents, which contain the Michael acceptor, are potent anticancer molecules by promoting intracellular reactive oxygen species (ROS) generation. In this study, we synthesized a panel of PL (piperlongumine) analogs with chlorine attaching at C2 and an electron-withdrawing/electron-donating group attaching to the aromatic ring. The results displayed that the strong electrophilicity group at the C2–C3 double bond of PL analogs plays an important role in the cytotoxicity whereas the electric effect of substituents, which attached to the aromatic ring, partly contributed to the anticancer activity. Moreover, the protein containing sulfydryl or seleno, such as TrxR, could be irreversibly inhibited by the C2–C3 double bond of PL analogs, and boost intracellular ROS generation. Then, the ROS accumulation could disrupt the redox balance, induce lipid peroxidation, lead to the loss of MMP (Mitochondrial Membrane Potential), and ultimately result in cell cycle arrest and A549 cell line death. In conclusion, PL analogs could induce in vitro cancer apoptosis through the inhibition of TrxR and ROS accumulation.

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Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway

Cited by 40 publications

References 40 publications

Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer

Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer

Schizandrin A induces the apoptosis and suppresses the proliferation, invasion and migration of gastric cancer cells by activating endoplasmic reticulum stress

Piperlongumine Analogs Promote A549 Cell Apoptosis through Enhancing ROS Generation

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