Activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway in human lung cancer cells by the new synthetic flavonoid, LZ-205

Zhang, Yi; Xu, Xuefen; Li, Wei; Hua, Miao; Huang, Shaoliang; Zhou, Yuxin; Sun, Yang; Li, Zhiyu; Guo, Qing; Zhao, Li

doi:10.18632/oncotarget.13535

Cited by 14 publications

(8 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Targeting ER stress can be a useful anti-cancer strategy. Recently, it was reported that some compounds exerts its proapoptotic effects by inducing ER stress in H460 and A549 cells [ 30 , 31 , 32 ]. In the present study, we observed an increasing of ER stress-related proteins such as ATF4 and p-EIF2α in a time- and dose-dependent manner, indicating that ER stress was activated after LicA treatment.…”

Section: Discussionmentioning

confidence: 99%

Licochalcone A Inhibits the Proliferation of Human Lung Cancer Cell Lines A549 and H460 by Inducing G2/M Cell Cycle Arrest and ER Stress

Qiu

Zhang

et al. 2017

IJMS

View full text Add to dashboard Cite

Licochalcone A (LicA), a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch, has wide spectrum of pharmacological activities. In this study, the anti-cancer effects and potential mechanisms of LicA in non-small cell lung cancer (NSCLC) cells were studied. LicA decreased cell viability and induced apoptosis in a dose-dependent manner in NSCLC cells. LicA inhibited lung cancer cells growth by blocking cell cycle progression at the G2/M transition and inducing apoptosis. LicA treatment decreased the expression of MDM2, Cyclin B1, Cdc2 and Cdc25C in H460 and A549 cancer cell lines. In addition, LicA induced caspase-3 activation and poly-ADP-ribose polymerase (PARP) cleavage, which displayed features of apoptotic signals. Furthermore, LicA increased the expression of endoplasmic reticulum (ER) stress related proteins, such as p-EIF2α and ATF4. These data provide evidence that LicA has the potential to be used in the treatment of lung cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Licochalcone A Inhibits the Proliferation of Human Lung Cancer Cell Lines A549 and H460 by Inducing G2/M Cell Cycle Arrest and ER Stress

Qiu

Zhang

et al. 2017

IJMS

View full text Add to dashboard Cite

show abstract

“…Alveolar cell apoptosis is a critical step in the pathogenesis of emphysema [ 36 , 37 ]. ER stress has been implicated in apoptotic signaling [ 7 ] and has been shown to regulate apoptosis in lung epithelial cells and human lung cancer cells [ 38 – 40 ]. Our results are in agreement with these studies in that downregulation of ER stress by 4-PBA decreased CS-induced cell apoptosis, thus preserving alveolar structure.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema

Wang

2017

Oncotarget

View full text Add to dashboard Cite

Chronic bronchitis and emphysema are pathologic features of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS)-induced endoplasmic reticulum (ER) stress has been implicated in the COPD development, but the molecular mechanism by which it contributes to COPD etiology and the specific role it plays in COPD pathogenesis remain poorly understood. Here, we aimed to determine the role of ER stress in the pathogenesis of CS-induced airway inflammation and emphysema. Exposure to CS significantly increased the expression of ER stress markers in Beas-2B cells and in mouse lungs, possibly through the production of oxidative stress. Further, inhibition of ER stress by 4-phenylbutyric acid (4-PBA) reduced CS extract-induced inflammation in Beas-2B cells through the modulation of NF-κB signaling. 4-PBA also protected against CS-induced airway inflammation and the development of emphysema in mice, which was associated with a reduction in NF-κB activation and alveolar cell apoptosis in the lungs. Taken together, our results suggest that ER stress is crucial for CS-induced inflammation and emphysema, and that targeting ER stress may represent a novel approach to the treatment of COPD.

show abstract

“…A persistent and overwhelming ER stress will lead to apoptosis. Several studies have reported that tocotrienols exert ER stress as one of the mechanisms to induce apoptosis [65,66,67]. In this section, the evidences of tocotrienols-induced ER stress are gathered and aligned to the present understanding on apoptosis that is led by ER stress (Figure 4).…”

Section: Tocotrienols Act As a Potent Apoptosis Inducermentioning

confidence: 86%

Tocotrienols Modulate a Life or Death Decision in Cancers

Tham

Loh

et al. 2019

IJMS

View full text Add to dashboard Cite

Malignancy often arises from sophisticated defects in the intricate molecular mechanisms of cells, rendering a complicated molecular ground to effectively target cancers. Resistance toward cell death and enhancement of cell survival are the common adaptations in cancer due to its infinite proliferative capacity. Existing cancer treatment strategies that target a single molecular pathway or cancer hallmark fail to fully resolve the problem. Hence, multitargeted anticancer agents that can concurrently target cell death and survival pathways are seen as a promising alternative to treat cancer. Tocotrienols, a minor constituent of the vitamin E family that have previously been reported to induce various cell death mechanisms and target several key survival pathways, could be an effective anticancer agent. This review puts forward the potential application of tocotrienols as an anticancer treatment from a perspective of influencing the life or death decision of cancer cells. The cell death mechanisms elicited by tocotrienols, particularly apoptosis and autophagy, are highlighted. The influences of several cell survival signaling pathways in shaping cancer cell death, particularly NF-κB, PI3K/Akt, MAPK, and Wnt, are also reviewed. This review may stimulate further mechanistic researches and foster clinical applications of tocotrienols via rational drug designs.

show abstract

Activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway in human lung cancer cells by the new synthetic flavonoid, LZ-205

Cited by 14 publications

References 39 publications

Licochalcone A Inhibits the Proliferation of Human Lung Cancer Cell Lines A549 and H460 by Inducing G2/M Cell Cycle Arrest and ER Stress

Licochalcone A Inhibits the Proliferation of Human Lung Cancer Cell Lines A549 and H460 by Inducing G2/M Cell Cycle Arrest and ER Stress

Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema

Tocotrienols Modulate a Life or Death Decision in Cancers

Contact Info

Product

Resources

About