A new molecular mechanism underlying the EGCG-mediated autophagic modulation of AFP in HepG2 cells

Zhao, Lin; Liu, Shengtang; Xu, Jia‐Ying; Li, Wei; Duan, Guangxin; Wang, Haichao; Yang, Huilin; Yang, Zaixing; Zhou, Ruhong

doi:10.1038/cddis.2017.563

Cited by 53 publications

(39 citation statements)

References 51 publications

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“…LC3 proteins have not been thoroughly explored by systematic biomolecular simulations or other computational structural methods. Among the simulations present in the literature, each one focused on specific aspects of LC3B dynamics using all-atom molecular dynamics (MD) simulations with a single force field (Jatana et al, 2019;Liu et al, 2013;Nuta et al, 2018;L. Zhao et al, 2017) or coarse-grained approaches (Thukral et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

The conformational and mutational landscape of the ubiquitin-like marker for the autophagosome formation in cancer

Fas

Kumar

Sora

et al. 2019

Preprint

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Autophagy is a cellular process to recycle damaged cellular components and its modulation can be exploited for disease treatments. A key autophagy player is a ubiquitin-like protein, LC3B. Compelling evidence attests the role of autophagy and LC3B in different cancer types. Many LC3B structures have been solved, but a comprehensive study, including dynamics, has not been yet undertaken. To address this knowledge gap, we assessed ten physical models for molecular dynamics for their capabilities to describe the structural ensemble of LC3B in solution using different metrics and comparison with NMR data. With the resulting LC3B ensembles, we characterized the impact of 26 missense mutations from Pan-Cancer studies with different approaches. Our findings shed light on driver or neutral mutations in LC3B, providing an atlas of its modifications in cancer. Our framework could be used to assess the pathogenicity of mutations by accounting for the different aspects of protein structure and function altered by mutational events.

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Section: Introductionmentioning

confidence: 99%

The conformational and mutational landscape of the ubiquitin-like marker for the autophagosome formation in cancer

Fas

Kumar

Sora

et al. 2019

Preprint

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“…EGCG has always achieved a milestone in the quest for cancer therapy. It has been observed to suppress breast cancer [5][6][7], prostate cancer [8][9][10], lung cancer [11][12][13], pancreatic cancer [14][15][16], and liver cancer [17,18]. All of this anticancer activity by EGCG has previously been demonstrated that EGCG is the most effective cancer chemopreventive polyphenol in green tea [19].…”

Section: Introductionmentioning

confidence: 88%

Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2α/ATF4 and IRE1α

Nesran

Shafie

Ishak

et al. 2019

BioMed Research International

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Epigallocatechin-3-gallate (EGCG) is the most abundant bioactive polyphenolic compound among the green tea constituents and has been identified as a potential anticancer agent in colorectal cancer (CRC) studies. This study was aimed to determine the mechanism of actions of EGCG when targeting the endoplasmic reticulum (ER) stress pathway in CRC. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed on HT-29 cell line and normal cell line (3T3) to determine the EGCG toxicity. Next, western blot was done to observe the expression of the related proteins for the ER stress pathway. The Caspase 3/7 assay was performed to determine the apoptosis induced by EGCG. The results demonstrated that EGCG treatment was toxic to the HT-29 cell line. EGCG induced ER stress in HT-29 by upregulating immunoglobulin-binding (BiP), PKR-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha subunit (eIF2α), activating transcription 4 (ATF4), and inositol-requiring kinase 1 alpha (IRE1α). Apoptosis was induced in HT-29 cells after the EGCG treatment, as shown by the Caspase 3/7 activity. This study indicates that green tea EGCG has the potential to inhibit colorectal cancer cells through the induction of ER stress.

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“…Western blot analysis. Protein extraction and western blot analyses were performed as previously described (26) Following 72 h of cell transfection with lentivirus, cells were seeded in 96-well plates at 5,000 cells/well. At the time of detection, 10 µl CCK-8 solution was added to each well, and the absorbance was measured at 450 nm using a microplate reader (Thermo Fisher Scientific, Inc.) after 90 min.…”

Section: Methodsmentioning

confidence: 99%

Placenta‑specific protein 8 promotes the proliferation of lung adenocarcinoma PC‑9 cells and their tolerance to an epidermal growth factor receptor tyrosine kinase inhibitor by activating the ERK signaling pathway

et al. 2019

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Placenta-specific protein 8 (PLAC8) is a conserved protein with a molecular weight of 12.5 kDa. The specific function of this protein has not been fully elucidated, however, PLAC8 has been found to play an important tumor regulatory role in certain types of cancer, including colon, pancreatic and liver cancer. PLAC8 also participates in the regulation of the cell cycle, autophagy, epithelial-mesenchymal transition and other cellular functions, indicating its potential as a molecular target worth further investigation. The present study investigated the effect of PLAC8 on the proliferation of lung adenocarcinoma PC-9 cells and their sensitivity to gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It was found that the inhibition of PLAC8 expression in PC-9 cells resulted in significantly decreased proliferation, whereas overexpression of PLAC8 significantly increased the proliferation (P<0.05) of PC-9 cells. Furthermore, inhibition of PLAC8 expression resulted in decreased activity of the ERK signaling pathway, while PLAC8 overexpression increased activity of this pathway. Inhibition of the ERK signaling pathway with U0126 reversed the effects induced by inhibiting or overexpressing PLAC8 on cell proliferation. In addition, overexpression of PLAC8 significantly decreased the sensitivity of PC-9 cells to gefitinib, and this effect was reversed by U0126. Overall, these results suggest that PLAC8 is involved in the regulation of proliferation of lung adenocarcinoma PC-9 cells and impacts their sensitivity to an EGFR-TKI. Thus, PLAC8 is a potential novel target in lung adenocarcinoma for future studies.

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A new molecular mechanism underlying the EGCG-mediated autophagic modulation of AFP in HepG2 cells

Cited by 53 publications

References 51 publications

The conformational and mutational landscape of the ubiquitin-like marker for the autophagosome formation in cancer

The conformational and mutational landscape of the ubiquitin-like marker for the autophagosome formation in cancer

Induction of Endoplasmic Reticulum Stress Pathway by Green Tea Epigallocatechin-3-Gallate (EGCG) in Colorectal Cancer Cells: Activation of PERK/p-eIF2α/ATF4 and IRE1α

Placenta‑specific protein 8 promotes the proliferation of lung adenocarcinoma PC‑9 cells and their tolerance to an epidermal growth factor receptor tyrosine kinase inhibitor by activating the ERK signaling pathway

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