ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer

Zou, Peng; Zhang, Junru; Xia, Yiqun; Kanchana, Karvannan; Guo, Gui-Long; Chen, Wenbo; Huang, Yi Wen; Wang, Zhe; Yang, Shulin; Liang, Guang

doi:10.18632/oncotarget.3333

Cited by 129 publications

(119 citation statements)

References 53 publications

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“…It has been reported that ROS generation can trigger cells apoptosis through activating both mitochondrial and ER stress pathways [9][10]. This is consistent with the fact that ROS generation can activate of JNK-mitochondrial and ER stress apoptotic pathways [20].…”

Section: Discussionsupporting

confidence: 83%

The antitumor effects of mitochondria-targeted 6-(nicotinamide) methyl coumarin

Wang

Yao

2016

Open Life Sciences

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Cancer is the second leading cause of death worldwide. Traditional antitumor drugs exhibit severe cytotoxic and side effects. Lung cancer needs new and more effective treatment approaches. Coumarin derivatives can act on various tumor cells and show anti-proliferative activity through various mechanisms, including mitochondrial signaling cascades that regulate development and apoptosis of cells. Mitochondria-targeted coumarin derivatives have not been reported yet. Taking advantage of the fact that cancer cells frequently have higher mitochondria membrane potential, we synthesized a mitochondria-targeted 6-(nicotinamide) methyl coumarin by coupling 6-methyl coumarin to nicotinamide. Our results demonstrate that 6-(nicotinamide) methyl coumarin preferentially kills A549 cells through inducing A549 cells apoptosis, mediated by increasing ROS level and causing mitochondrial depolarization. Strikingly, the viability of the A31 cells treated with 6-(nicotinamide) methyl coumarin did not decrease, indicating that 6-(nicotinamide) methyl coumarin preferentially accumulates in A549 cells and A549 cells are much more susceptible to 6-(nicotinamide) methyl coumarin treatment compared with A31 cells.

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Section: Discussionsupporting

confidence: 83%

The antitumor effects of mitochondria-targeted 6-(nicotinamide) methyl coumarin

Wang

Yao

2016

Open Life Sciences

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“…Induction of intracellular ROS generation can trigger cell apoptosis via the ER stress pathway29. We previously found that fucoidan induces ROS and ER stress in lung cancer cells.…”

Section: Resultsmentioning

confidence: 99%

“…However, induction of excess ROS in cancer cells via therapeutic approaches, such as chemotherapy and radiotherapy, may trigger ROS-mediated cell death mechanisms39. ROS induce ER stress through modification of proteins and lipids29. Here, we examined effects of fucoidan on ROS-mediated ER stress and apoptosis, developing a potential therapeutic strategy for the treatment of lung cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Fucoidan induces Toll-like receptor 4-regulated reactive oxygen species and promotes endoplasmic reticulum stress-mediated apoptosis in lung cancer

Hsu

Lin

et al. 2017

Sci Rep

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Fucoidan, a sulfated polysaccharide extracted from brown algae, exhibits anti-cancer activity. However, the effects and mechanism of fucoidan-induced apoptosis via endoplasmic reticulum (ER) stress is unclear. In this study, we demonstrated that fucoidan prevents tumorigenesis and reduces tumor size in LLC1-xenograft male C57BL/6 mice. Fucoidan induces an ER stress response by activating the PERK-ATF4-CHOP pathway, resulting in apoptotic cell death in vitro and in vivo. Furthermore, ATF4 knockdown abolishes fucoidan-induced CHOP expression and rescues cell viability. Specifically, fucoidan increases intracellular reactive oxygen species (ROS), which increase ATF4 and CHOP in lung cancer cells. Using the ROS scavenger N-acetyl-l-cysteine (NAC), we found that ROS generation is involved in fucoidan-induced ER stress-mediated apoptosis. Moreover, via Toll-like receptor 4 (TLR4) knockdown, we demonstrated that fucoidan-induced ROS and CHOP expression were attenuated. Our study is the first to identify a novel mechanism for the antitumor activity of fucoidan. We showed that fucoidan inhibits tumor viability by activating the TLR4/ROS/ER stress axis and the downstream PERK-ATF4-CHOP pathway, leading to apoptosis and suppression of lung cancer cell progression. Together, these results indicate that fucoidan is a potential preventive and therapeutic agent for lung cancer that acts via activation of ROS-dependent ER stress pathways.

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“…Koprowski et al revealed that curcumin could induce growth suppression and apoptosis of cholangiocarcinoma at low treatment concentrations (30). Zou et al reported that an analog of curcumin, WZ35, exhibited the anticancer effect on gastric cancer via activation of the JNK and ER stress apoptotic pathways mediated by ROs generation (31).…”

Section: Discussionmentioning

confidence: 99%

Curcumin induces apoptotic cell death and protective autophagy in human gastric cancer cells

Zhou

Yang

et al. 2017

Oncology Reports

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Abstract. Curcumin possesses an anticancer effect against a wide assortment of tumors with selective cytotoxicity for tumor cells. However, the mechanism involved in the curcumin-induced anticancer effect remain unclear. In the present study, we investigated the efficacy of curcumin against human gastric cancer cell growth and the molecular mechanism involved. Our results demonstrated that curcumin inhibited the viabilities of gastric cancer cell lines BGC-823, SGC-7901 and MKN-28 in both a time-and dose-dependent manner. In addition, curcumin treatment induced gastric cancer cell apoptosis in a dose-responsive manner. Western blotting of apoptosis-related proteins further confirmed the pro-apoptotic potential of curcumin. After exposure to curcumin, a robust induction of autophagy was observed in gastric cancer cells, which was characterized by the formation of acidic vesicular organelles (AVOs), conversion of LC3-I to LC3-II and an increase in the levels of autophagy-related proteins. Activation of the PI3K/Akt/mTOR signaling pathway was suppressed in gastric cancer cells with curcumin treatment. However, administration of the autophagy inhibitor 3-methyladenine (3-MA) significantly promoted the apoptotic cell death induced by curcumin. Collectively, our findings provide new evidence that curcumin induces apoptotic cell death and protective autophagy in human gastric cancer cells in vitro. Autophagy inhibitor treatment may provide a novel and effective strategy for improving the anticancer effect of curcumin against gastric cancer.

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ROS generation mediates the anti-cancer effects of WZ35 via activating JNK and ER stress apoptotic pathways in gastric cancer

Cited by 129 publications

References 53 publications

The antitumor effects of mitochondria-targeted 6-(nicotinamide) methyl coumarin

The antitumor effects of mitochondria-targeted 6-(nicotinamide) methyl coumarin

Fucoidan induces Toll-like receptor 4-regulated reactive oxygen species and promotes endoplasmic reticulum stress-mediated apoptosis in lung cancer

Curcumin induces apoptotic cell death and protective autophagy in human gastric cancer cells

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