Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release

Liao, Chien-Chang; Zheng, Kai; Li, Yan; Xu, Hong; Kang, Qiangrong; Liu, Fan; Hu, Xiaopeng; Jin, Zhe; Zeng, Yong; Kong, Xiaoli; Zhang, Jian; Wu, Xuli; Wu, Haiqiang; Liu, Lizhong; Xiao, Xiaohua; Wang, Yifei; He, Zhendan

doi:10.18632/oncotarget.10159

Cited by 22 publications

(22 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endoplasmic reticulum and mitochondrial are important organelles to maintain normal cell function (Nami et al, ; Liao et al, ). The unfolded protein response (UPR) is a cellular signaling pathway in the ER that is activated in response to overloading of unfolded or misfolded peptide chains.…”

Section: Introductionmentioning

confidence: 99%

Matrine Suppresses the ER-positive MCF Cells by Regulating Energy Metabolism and Endoplasmic Reticulum Stress Signaling Pathway

Xiao

Wang

et al. 2017

Phytother. Res.

View full text Add to dashboard Cite

Matrine (C H N O), an alkaloid that is one of the main active components from Sophora flavescens. Matrine has been demonstrated to have therapeutic effects on various solid tumors, including breast cancer, but the mechanism still needs further study. Endoplasmic reticulum (ER)-positive Michigan Cancer Foundation cells were cultured, and matrine was added in various amounts to measure the dose-dependent and time-dependent cytotoxicity. Hoechst 33258 staining was used to observed nuclear morphological changes. Apoptosis was measured by AnnexinV/PI double staining assay kit. Intracellular adenosine triphosphate and glycometabolism were detected by assay kit. The protein levels GRP78, p-eIF2α, CHOP, cytochrome c, and HexokinaseII were analyzed. Mechanistic investigations revealed that matrine treatment causes ER dilation and up-regulated the expression of ER stress markers GRP78, eIF2α, and CHOP, increases the levels of apoptotic in Michigan Cancer Foundation cells, subsequently, blocking the ER stress-mediated apoptosis pathway, significantly decreased matrine-induced apoptotic but still has significant difference between control group. In addition, matrine not only promoted the occurrence of ER stress but also inhibited the expression of hexokinase II, down-regulated energy metabolism. In summary, the present study suggests that the induction of ER stress-mediated apoptosis by matrine and down-regulated energy metabolism may account for its cytotoxic effects in human breast cancer cells. Copyright © 2017 John Wiley & Sons, Ltd.

show abstract

Section: Introductionmentioning

confidence: 99%

Matrine Suppresses the ER-positive MCF Cells by Regulating Energy Metabolism and Endoplasmic Reticulum Stress Signaling Pathway

Xiao

Wang

et al. 2017

Phytother. Res.

View full text Add to dashboard Cite

show abstract

“…During the course of tumor development, the metabolic pathway of protein metabolism is often disordered, and intracellular homeostasis is disrupted. 31 It has been reported that PSMD4 plays an important role in ubiquitination-related protein metabolism. 21 Studies of patients with multiple myeloma have found that PSMD4 may be associated with adverse outcomes and resistance to bortezomib.…”

Section: Discussionmentioning

confidence: 99%

PSMD4 regulates the malignancy of esophageal cancer cells by suppressing endoplasmic reticulum stress

Zhao

et al. 2019

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

Proteasome 26S subunit non‐ATPase 4 (PSMD4) is an important proteasome ubiquitin receptor and plays a key role in endoplasmic reticulum stress (ERS). However, the study of PSMD4 in esophageal cancer (EC) is relatively rare. Here, we found that the expression of PSMD4 was markedly enhanced in EC tissues and cell lines. The cell counting kit‐8 (CCK‐8) assay showed that overexpression of PSMD4 significantly enhanced Eca109 cell viability, while inhibition of PSMD4 reduced Eca109 cell viability. Knockdown of PSMD4 induced Eca109 cell apoptosis and cell cycle arrest. More importantly, knockdown of PSMD4 significantly enhanced the expression of glucose regulated protein 78, activating transcription factor 6, and p‐protein kinase R‐like ER kinase, indicating an enhanced ERS response in esophageal cancer cells. Compared with the control cells, brefeldin A significantly inhibited the expression of PSMD4 and increased the expression of p53‐upregulated modulator of apoptosis. However, such effects were largely reversed after overexpressing PSMD4 in Eca109 cells, suggesting that silencing PSMD4 could enhance ERS‐induced cell apoptosis. In summary, upregulation of PSMD4 promoted the progression of esophageal cancer mainly by reducing ERS‐induced cell apoptosis.

show abstract

“…The level of Ca 2+ in cytoplasm was elevated which showed that intrinsic apoptosis was induced. Release of Ca 2+ from endoplasmic reticulum revealed that ER stress may be involved in apoptosis, while further study was still needed to confirm this hypothesis [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Aqueous Extracts ofCordyceps kyushuensisKob Induce Apoptosis to Exert Anticancer Activity

Zhao

Zhang

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Cancer has become the leading cause of mortality since 2010 in China. Despite the remarkable advances in cancer therapy, a low survival rate is still a burden to the society. The antineoplastic activity of aqueous extracts of Cordyceps kyushuensis Kob (AECK) was measured in this study. Results showed that AECK can significantly inhibit the proliferation and viability of U937 and K562 when treated with different concentrations of AECK, and the IC50 values of U937 and K562 were 31.23 μg/ml and 62.5 μg/ml, respectively. Hoechst 33258 staining showed that AECK could cause cell shrinkage, chromatin, condensation, and cytoplasmic blebbing, and DNA ladder experiment revealed the evident feature of DNA fragmentation which showed that AECK could induce cell apoptosis. Moreover, AECK gave rise to intrinsic apoptosis through increasing the amount of Ca2+ and downregulating the expression of Bcl-2. Meanwhile, the level of Fas death receptor was elevated which indicated that AECK could lead to exogenous apoptosis in U937. The expressions of oncogene c-Myc and c-Fos were suppressed which manifested that AECK could negatively regulate the growth, proliferation, and tumorigenesis of U937 cells. This research presented the primary antitumor activity of AECK which would contribute to the widely use of Cordyceps kyushuensis Kob as a functional food and medicine.

show abstract

Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release

Cited by 22 publications

References 51 publications

Matrine Suppresses the ER-positive MCF Cells by Regulating Energy Metabolism and Endoplasmic Reticulum Stress Signaling Pathway

Matrine Suppresses the ER-positive MCF Cells by Regulating Energy Metabolism and Endoplasmic Reticulum Stress Signaling Pathway

PSMD4 regulates the malignancy of esophageal cancer cells by suppressing endoplasmic reticulum stress

Aqueous Extracts ofCordyceps kyushuensisKob Induce Apoptosis to Exert Anticancer Activity

Contact Info

Product

Resources

About