EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy

Satoh, Motohiko; Takemura, Yukie; Hamada, Hironobu; Sekido, Yoshitaka; Kubota, Shunichiro

doi:10.1186/1475-2867-13-19

Cited by 60 publications

(49 citation statements)

References 37 publications

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“…Interestingly; the observed increase in proliferation inhibition was not associated with apoptosis induction. These observations are in contrast with some published studies, which show an association between autophagy inhibition and enhanced apoptosis [33, 53]. On the other hand, our results suggest that autophagy inhibition synergizes with Nx (to prevent autophagy activation) resulting in enhanced proliferation inhibition rather than apoptosis activation.…”

Section: Discussioncontrasting

confidence: 99%

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STAT3 down regulates LC3 to inhibit autophagy and pancreatic cancer cell growth

Gong

Muñoz

Chan³

et al. 2014

Oncotarget

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The dismal 5-year survival (<5%) for pancreatic cancer (PanCA) underscores the need for developing effective therapeutic options. Recent studies from our laboratory have shown that Nexrutine® (Nx), a bark extract from Phellodendron amurense exhibits excellent anticancer activity in human pancreatic cancer cells through inhibition of inflammatory signaling via STAT3/NFκB/Cox-2. Given the apparent high oxidative stress and autophagic activity in pancreatic tumors, we investigated the potential of Nx to modulate autophagy, reactive oxygen species (ROS), and their crosstalk. Our results show that Nx inhibits autophagy and decreases ROS generation. Pharmacological inhibition of autophagy led to decreased ROS generation and proliferation with no significant effect on apoptosis. Further, using combination index analysis we also found that combination of late-stage autophagy inhibitor with Nx exhibited a moderate synergistic to additive effect. Additionally, genetic or pharmacological inactivation of STAT3 reduced LC3-II levels and expression indicating a possible role for STAT3 in transcriptional regulation of autophagy. Since both inflammatory and oxidative stress signaling activate STAT3, our data implicates that STAT3 plays a vital role in the regulation of autophagy through its contributions to the positive feedback loop between ROS and autophagy. Overall, our findings reveal an important role for STAT3/LC3/ROS in Nx-mediated anti-pancreatic cancer effects.

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Section: Discussioncontrasting

confidence: 99%

“…It is well established that autophagy and ROS can facilitate cell death or cell survival depending on the nature of stimuli and cellular context [6, 53]. Given our observation of reduced intracellular ROS levels upon autophagy inhibition, we tested the impact of autophagy on Nx induced anti-proliferative activities.…”

Section: Discussionmentioning

confidence: 99%

STAT3 down regulates LC3 to inhibit autophagy and pancreatic cancer cell growth

Gong

Muñoz

Chan³

et al. 2014

Oncotarget

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“…Previously, it has been shown that a high concentration (50 -100 M) of EGCG stimulates autophagy leading to cell death in cancer cells (44,45). Another study reported that EGCG stimulates autophagy, which leads to inhibition of endotoxin-induced septic shock through EGCG-induced degradation of HMGB1, a late lethal inflammatory factor (46).…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin Gallate (EGCG) Stimulates Autophagy in Vascular Endothelial Cells

Kim

Montana

Jang

et al. 2013

Journal of Biological Chemistry

165

130

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Background: Green tea polyphenol (EGCG) has beneficial effects on cardiovascular dysfunction. Results: EGCG stimulates autophagy through a CaMKK␤-mediated mechanism, which contributes to degradation of lipid droplets. Conclusion: Regulation of autophagic flux by EGCG plays a role in intracellular lipid accumulation. Significance: Findings show a novel mechanism for beneficial effects of EGCG in cardiovascular complications.

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“…Reactive oxygen species (ROS) were reported to be responsible for EGCG-induced apoptosis in mesothelioma (27) and EGCG-induced ROS production in endometrial carcinoma cells (28). However, ROS were not involved in EGCG-induced apoptosis in human laryngeal epidermoid carcinoma (Hep2) cells (14), although EGCG reduced deoxynivalenol-induced ROS in HT-29 cells (29).…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism of epigallocatechin-3-gallate in human esophageal squamous cell carcinoma in vitro and in vivo

Liu

Hou

et al. 2014

Oncology Reports

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Abstract. Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, has been shown to inhibit proliferation in various types of tumors. However, few studies concerning the role and mechanism of EGCG in esophageal squamous cell carcinoma are available. Therefore, the antitumor mechanism of EGCG needs to be investigated. The present study aimed to examine the antitumor effect of EGCG on the human esophageal squamous cell carcinoma cell lines, Eca-109 and Te-1, in vitro and in vivo. Cell viability was assessed using the MTT assay and tumor formation and growth in murine xenograft models with or without EGCG treatment. Cell cycle analysis and levels of reactive oxygen species (ROS) were detected using flow cytometry. Apoptosis was measured by Annexin/propidium iodide staining. Caspase-3 cleavage and vascular endothelial growth factor (VEGF) expression were detected using western blot analysis and immunohistochemistry in tumor cell lines and tumor xenografts, respectively. The results showed that EGCG inhibited proliferation in the Eca-109 and Te-1 cells in a time-and dose-dependent manner. Tumor cells were arrested in the G 1 phase and apoptosis was accompanied by ROS production and caspase-3 cleavage. In a mouse model, EGCG significantly inhibited the growth of Eca-109 tumors by increasing the expression of cleaved-caspase-3 and decreasing VEGF protein levels. Taken together, the results suggest that EGCG inhibits proliferation and induces apoptosis through ROS production, caspase-3 activation, and a decrease in VEGF expression in vitro and in vivo. Furthermore, EGCG may have future clinical applications for novel approaches to treat esophageal squamous cell carcinoma.

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EGCG induces human mesothelioma cell death by inducing reactive oxygen species and autophagy

Cited by 60 publications

References 37 publications

STAT3 down regulates LC3 to inhibit autophagy and pancreatic cancer cell growth

STAT3 down regulates LC3 to inhibit autophagy and pancreatic cancer cell growth

Epigallocatechin Gallate (EGCG) Stimulates Autophagy in Vascular Endothelial Cells

Molecular mechanism of epigallocatechin-3-gallate in human esophageal squamous cell carcinoma in vitro and in vivo

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