PERK/eIF-2α/CHOP Pathway Dependent ROS Generation Mediates Butein-induced Non-small-cell Lung Cancer Apoptosis and G2/M Phase Arrest

Ma, Zhiqiang; Li, Mingyang; Guo, Kai; Han, Donghui; Li, Xiaofei; Mu, Deguang; Yan, Xiaolong

doi:10.7150/ijbs.33790

Cited by 37 publications

(37 citation statements)

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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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“…Further it exerted a dose-dependent effect on focal adhesion kinase, Akt, and ERK phosphorylation in B16F10 cells. In addition, its treatment led to the inhibition of cell adhesion, migration and invasion of NSCLC cells (Di et al, 2019). Zhang et al, (2008) also reported this compound to inhibit the migration as well as invasion of bladder cancer cells by modulating ERK1/2 and NF-kB signaling.…”

Section: Discussionmentioning

confidence: 94%

“…In addition, butein was also reported to exert its antiproliferative and pro-apoptotic effect through inhibition of NF-κB, AP-1 and Akt signaling in HTLV-1infected T cells in both in vitro and in vivo settings clearly indicating its therapeutic potential against adult T-cell leukemia/lymphoma (Ishikawa et al, 2017). Besides, this flavonoid induced apoptosis and arrest at the G2/M phase of cell cycle through PERK/eIF-2α/CHOP pathway dependent ROS generation (Di et al, 2019).…”

Section: Discussionmentioning

confidence: 98%

An Investigation on the Therapeutic Potential of Butein, A Tretrahydroxychalcone Against Human Oral Squamous Cell Carcinoma

Bordoloi

Monisha

Roy

et al. 2019

Asian Pac J Cancer Prev

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Background: Oral squamous cell carcinoma (OSCC) is one of the most predominant cancers in India. With advances in the field of oncology, a number of therapies have emerged; however, they are minimally effective. Consequently, there is a need to develop safe and effective regimens for the treatment of OSCC. Butein, a tetrahydroxychalcone has been found to exhibit potent antioxidant, anti-inflammatory, and also anti-tumor effects against several cancer types. However, its effect on OSCC is not studied yet. Methods: The effect of butein on the viability, apoptosis, migration and invasion of OSCC cells was evaluated using MTT, colony formation, PI/FACS, live and dead, scratch wound healing, and matrigel invasion assays. Further Western blot analysis was done to evaluate the expression of different proteins involved in the regulation of cancer hallmarks. Results: This is the first report exemplifying the anti-cancer effect of butein against OSCC. Our results showed that butein exhibited potent anti-proliferative, cytotoxic, anti-migratory, and anti-invasive effects in OSCC cells. It suppressed the expression of NF-κB and NF-κB-regulated gene products such as COX-2, survivin and MMP-9 which are involved in the regulation of different processes like proliferation, survival, invasion, and metastasis of OSCC cells. Conclusion Collectively, these results suggest that butein has immense potential in the management of OSCC. Nonetheless, in vivo validation is critical before moving to clinical trials.

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“…Literatures have demonstrated that butein exposure can increase ROS generation in several tumor cell lines 31‐33 . To further clarify whether p53 was activated through ROS generation in butein‐treated U‐2 OS cells, we first evaluate the level of ROS in these cells using 2′,7′‐dichlorofluorescin diacetate (DCFDA) and MitoSOX Red staining.…”

Section: Resultsmentioning

confidence: 99%

“…Butein inhibits hepatocellular carcinoma growth via the down‐regulation of Aurora B kinase activity 35 . Butein suppresses the cell viability of non‐small cell lung cancer through ER stress‐dependent ROS generation and apoptosis pathway 31 . Butein inhibits cell proliferation and glycolysis in hepatocellular carcinoma through suppressing epidermal growth factor receptor (EGFR) signaling pathway 36 .…”

Section: Discussionmentioning

confidence: 99%

Butein induces cellular senescence through reactive oxygen species‐mediated p53 activation in osteosarcoma U‐2 OS cells

Hsu

Chen

et al. 2020

Environmental Toxicology

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Butein is a flavonoid isolated from various medicinal plants. It is known to have different biological activities including anti‐inflammation, anti‐adipogenesis, and anti‐angiogenesis. In the study, we demonstrated the anti‐proliferative effect of butein in human osteosarcoma U‐2 OS cells. Our data showed that butein significantly suppressed the viability and colony formation ability of U‐2 OS cells. Further experiments revealed butein exposure resulted in a cell cycle arrest at S and G2/M phase in U‐2 OS cells. Importantly, we found that butein activated the tumor suppressor p53, and trigged a p53‐dependent senescence in U‐2 OS cells. Knockdown of p53 suppressed the senescence and rescued the viability in butein‐treated U‐2 OS cells. Furthermore, we observed that butein exposure significantly enhanced reactive oxygen species (ROS) levels in U‐2 OS cells. Co‐administration of the ROS inhibitor NAC largely abolished the up‐regulated p53 protein level, and rescued the suppressed viability and colony formation ability in butein‐exposed U‐2 OS cells. Taken together, our data proposed the increased ROS by butein exposure activated p53, and the activated p53 was involved in the anti‐proliferative effect of butein via inducing senescence in U‐2 OS cells. This report suggests that butein is a promising candidate for cancer therapy against osteosarcoma.

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PERK/eIF-2α/CHOP Pathway Dependent ROS Generation Mediates Butein-induced Non-small-cell Lung Cancer Apoptosis and G2/M Phase Arrest

Cited by 37 publications

References 50 publications

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

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

An Investigation on the Therapeutic Potential of Butein, A Tretrahydroxychalcone Against Human Oral Squamous Cell Carcinoma

Butein induces cellular senescence through reactive oxygen species‐mediated p53 activation in osteosarcoma U‐2 OS cells

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