A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells

Qiu, Mingning; Chen, Lieqian; Tan, Guobin; Ke, Longzhi; Zhang, Sai; Chen, Hege; Liu, Jianjun

doi:10.1038/srep15104

Cited by 60 publications

(47 citation statements)

References 30 publications

(37 reference statements)

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“…Therefore, targeting ROS is an important anticancer therapeutic strategy. In fact, a large number of studies have demonstrated the induction of ROS-mediated apoptosis by various therapeutic drugs [19-21]. In this study, we found that LA triggered ROS generation (Fig.…”

Section: Discussionsupporting

confidence: 60%

Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells

Yang¹,

Zhang²,

Wang³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Levistolide A (LA), a natural compound isolated from the traditional Chinese herb Ligusticum chuanxiong Hort, is used for treating cancer. In this study, we investigated the anticancer effect of LA in HCT116 and its isogenic p53-/- colon cancer cells, as well as the underlying mechanisms. Methods: MTT assay was used to evaluate the effect of LA on the viability of cancer cells. Apoptosis and reactive oxygen species (ROS) production by the cells were determined by flow cytometry. Protein expression was detected by western blotting. Results: The results showed that LA inhibited viability and caused apoptosis of both wild-type and p53-/- HCT116 cells. LA was able to trigger production of ROS and endoplasmic reticulum (ER) stress. Inhibition of ROS using N-acetylcysteine abrogated LA-induced ER stress and apoptosis, as well as the reduction in cancer cell viability. Conclusion: Our results indicate that LA causes apoptosis of colon cancer cells via ROS-mediated ER stress pathway. It will be interesting to develop the natural compound for chemotherapy of cancers such as CRC.

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Section: Discussionsupporting

confidence: 60%

Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells

Yang¹,

Zhang²,

Wang³

et al. 2017

Cell Physiol Biochem

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“…Low to moderate ROS levels may induce tumorigenesis, but excessive ROS generation promotes cancer cell apoptosis. Therefore, targeting ROS is a vital therapeutic approach in multiple cancers through the induction of ROS‐mediated cell death . Herein, CGs were found to increase the production of ROS in both Huh‐7 and HepG2 cells in a dose‐dependent manner, which may lead to an imbalance of redox reactions, and induction of apoptosis after TRAIL treatment.…”

Section: Discussionmentioning

confidence: 94%

Cardiac glycoside sensitized hepatocellular carcinoma cells to TRAIL via ROS generation, p38MAPK, mitochondrial transition, and autophagy mediation

Rasheduzzaman

Yin

Park

2019

Molecular Carcinogenesis

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A major concern in the clinical application of tumor necrosis factor related apoptosis‐inducing ligand (TRAIL) in tumors is the development of resistance. Therefore, agents that can potentially restore TRAIL sensitivity are important therapeutic targets for cancer treatment. Herein, we evaluated lanatoside c and digoxin, both of which are widely used cardiac glycosides (CGs), for their ability to sensitize human hepatocellular carcinoma cells (Huh‐7 and HepG2) through TRAIL‐induced apoptosis. CGs functionalize TRAIL as shown by its effect on intracellular reactive oxygen species (ROS) generation, which damages mitochondrial integrity and thereby confers intrinsic apoptotic caspase cascade during combined treatment. Caspase activation is dependent on ROS as shown by the ability of CGs to generate ROS and the ROS‐N‐acetylcysteine (NAC) relationship, which inhibits apoptosis during cotreatment by preventing the formation of caspase‐8 and ‐3. Furthermore, CGs triggered p38MAPK phosphorylation and NAC pre‐exposure blocked p38MAPK phosphorylation, which demonstrated that p38MAPK was dependent upon ROS generation. Additionally, CGs were found to be potent inducers of AMPK‐mediated protective autophagy as pharmacological and genetic autophagy inhibition reached the higher threshold of TRAIL‐mediated apoptosis. Finally, CGs downregulated the expression of the antiapoptotic protein Bcl‐2 and increased the translocation of proapoptotic protein cytochrome c, thereby inducing apoptosis. Collectively, these results indicate that CGs potentiate the enhanced cytotoxic capacity to TRAIL through ROS generation, p38MAPK phosphorylation, cell survival protein downregulation, and protective autophagy inhibition.

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“…The generation of ROS exhibit a close correlation with tumour cell death3641. To identify roles of intracellular ROS in SHK-induced gastric cancer cell death, ROS scavengers N-acetyl-L-cysteine (NAC) and L-glutathione (GSH) were used.…”

Section: Resultsmentioning

confidence: 99%

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

Liang

Cai

Chen³

et al. 2016

Sci Rep

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The prognosis of gastric cancer remains poor due to clinical drug resistance. Novel drugs are urgently needed. Shikonin (SHK), a natural naphthoquinone, has been reported to trigger cell death and overcome drug resistance in anti-tumour therapy. In this study, we investigated the effectiveness and molecular mechanisms of SHK in treatment with gastric cancer. In vitro, SHK suppresses proliferation and triggers cell death of gastric cancer cells but leads minor damage to gastric epithelial cells. SHK induces the generation of intracellular reactive oxygen species (ROS), depolarizes the mitochondrial membrane potential (MMP) and ultimately triggers mitochondria-mediated apoptosis. We confirmed that SHK induces apoptosis of gastric cancer cells not only in a caspase-dependent manner which releases Cytochrome C and triggers the caspase cascade, but also in a caspase-independent manner which mediates the nuclear translocation of apoptosis-inducing factor and Endonuclease G. Furthermore, we demonstrated that SHK enhanced the chemotherapeutic sensitivity of 5-fluorouracil and oxaliplatin in vitro and in vivo. Taken together, our data show that SHK may be a novel therapeutic agent in the clinical treatment of gastric cancer.

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A reactive oxygen species activation mechanism contributes to JS-K-induced apoptosis in human bladder cancer cells

Cited by 60 publications

References 30 publications

Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells

Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells

Cardiac glycoside sensitized hepatocellular carcinoma cells to TRAIL via ROS generation, p38MAPK, mitochondrial transition, and autophagy mediation

Shikonin induces mitochondria-mediated apoptosis and enhances chemotherapeutic sensitivity of gastric cancer through reactive oxygen species

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