Activation of ERK–p53 and ERK-Mediated Phosphorylation of Bcl-2 Are Involved in Autophagic Cell Death Induced by the c-Met Inhibitor SU11274 in Human Lung Cancer A549 Cells

Liu, Ying; Yang, Ying; Ye, Yuanchao; Shi, Qi-Feng; Chai, Kuan; Tashiro, Shin‐ichi; Onodera, Satoshi; Ikejima, Takashi

doi:10.1254/jphs.11181fp

Cited by 60 publications

(59 citation statements)

References 42 publications

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“…The MDC staining further confirmed a marked activity of autophagy with accumulation of autophagosomes in MCF-7 cells following CVB-D treatment. It's known that LC3, a mammalian homologue of ATG8 essential for autophagy in yeast, is recruited to the autophagosome membrane in an ATG5-dependent manner (21). Therefore, autophagosome membrane association of LC3 is a specific marker for autophagy.…”

Section: Discussionmentioning

confidence: 99%

“…This conversion is considered a reliable marker of autophagy (21). MCF-7 cells plated on coverslips were fixed in 4% paraformaldehyde.…”

Section: Immunofluorescence Assaymentioning

confidence: 99%

“…LC3, a microtubule-associated protein, is lipidated upon activation of autophagy and associated with the autophagosome membrane (21). To investigate if LC3 was involved in CVB-D-induced autophagy, LC3 puncta formation was assessed by immunofluorescence (IF).…”

Section: Involvement Of Lc3 and Atg5 In Cvb-d-treated Mcf-7 Cellsmentioning

confidence: 99%

“…3: C and D), indicating the recruitment of LC3 in CVB-D-induced autophagy. It is well known that the conversion from LC3-I to LC3-II is a reliable marker of autophagy, and ATG5 is essential for autophagosome formation (21). To further assess autophagy activation in this case, MCF-7 cells following CVB-D treatment were incubated with anti-LC3 and anti-ATG5 antibodies, respectively.…”

Section: Involvement Of Lc3 and Atg5 In Cvb-d-treated Mcf-7 Cellsmentioning

confidence: 99%

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Cyclovirobuxine D Induces Autophagy-Associated Cell Death via the Akt/mTOR Pathway in MCF-7 Human Breast Cancer Cells

Sun

Gao

et al. 2014

J Pharmacol Sci

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Abstract. Autophagy is a highly regulated and multi-step biological process that serves to remove damaged cytoplasmic components and organelles. It has been suggested that the activation of autophagy may be a promising therapeutic strategy for cancer treatment by triggering cell death. In this study, we reported that cyclovirobuxine D (CVB-D), an alkaloid component in a traditional Chinese herb, could induce autophagy in the MCF-7 human breast cancer cell line. CVB-D inhibited the viability of MCF-7 cells in a concentration-and time-dependent manner. Activation of autophagy was characterized by transmission electron microscopy, monodansylcadaverine staining, and expression of autophagy marker microtubule-associated protein 1 light chain 3 (LC3). After CVB-D treatment, a clear accumulation of autophagosomes was observed accompanied with elevated LC3 fluorescent puncta. Western blot analysis revealed that CVB-D significantly promoted the conversion from LC3-I to LC3-II and the expression of autophagy-related protein 5 (ATG5), which are both essential for autophagosome formation. On the other hand, CVB-D-induced autophagy and decrease in cell viability could be blocked by 3-methyladenine, a well-established autophagy inhibitor. Moreover, CVB-D attenuated the phosphorylation of Akt and mTOR, two pivotal suppressors in autophagy pathways. These findings shed new light on the pharmacological actions and mechanism of CVB-D and may support the potential utility of autophagy inducers in cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

“…This conversion is considered a reliable marker of autophagy (21). MCF-7 cells plated on coverslips were fixed in 4% paraformaldehyde.…”

Section: Immunofluorescence Assaymentioning

confidence: 99%

Section: Involvement Of Lc3 and Atg5 In Cvb-d-treated Mcf-7 Cellsmentioning

confidence: 99%

Section: Involvement Of Lc3 and Atg5 In Cvb-d-treated Mcf-7 Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Cyclovirobuxine D Induces Autophagy-Associated Cell Death via the Akt/mTOR Pathway in MCF-7 Human Breast Cancer Cells

Sun

Gao

et al. 2014

J Pharmacol Sci

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show abstract

“…PD98059 is an inhibitor of the extracellular signal-related kinase (ERK) pathway (20). Regucalcin mRNA expression in NRK52E cells is not altered in the presence of PD98059 in vitro (12), suggesting that its expression is not mediated through a MAPK that is related to the ERK pathway.…”

Section: Various Factors Regulate Regucalcin Gene Expressionmentioning

confidence: 99%

The potential role of regucalcin in kidney cell regulation: Involvement in renal failure (Review)

Yamaguchi

2015

International Journal of Molecular Medicine

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Abstract. The kidneys play a physiologic role in the regulation of urine formation and nutrient reabsorption in the proximal tubule epithelial cells. Kidney development has been shown to be regulated through calcium (Ca 2+ ) signaling processes that are present through numerous steps of tubulogenesis and nephron induction during embryonic development of the kidneys. Ca 2+ -binding proteins, such as calbindin-D28k and regucalcin are important proteins that are commonly used as biomarkers in pronephric tubules, and the ureteric bud and metanephric mesenchyme. Previous research on regucalcin focused on Ca 2+ sensors that are involved in renal organogenesis and the link between Ca 2+ -dependent signals and polycystins. Moreover, regucalcin has been highlighted to play a multifunctional role in kidney cell regulation. The regucalcin gene, which is localized on the X chromosome, is regulated through various transcription factors. Regucalcin has been found to regulate intracellular Ca 2+ homeostasis in kidney proximal tubule epithelial cells. Regucalcin has been demonstrated to regulate the activity of various enzymes that are involved in intracellular signaling pathways. It has been noted that regucalcin suppresses DNA synthesis and regulates the gene expression of various proteins related to mineral transport, transcription factors, cell proliferation and apoptosis. The overexpression of regucalcin has been shown to exert suppressive effects on cell proliferation and apoptotic cell death, which are stimulated by various stimulatory factors. Moreover, regucalcin gene expression was found to to be involved in various pathophysiological states, including renal failure. This review discusses recent findings concerning the potential role of regucalcin as a regulatory protein in the kidney proximal tubule epithelial cells.

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Magnesium isoglycyrrhizinate promotes the activated hepatic stellate cells apoptosis via endoplasmic reticulum stress and ameliorates fibrogenesis in vitro and in vivo

et al. 2017

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Varied pathogenetic elements have been touched upon the liver fibrosis, including inflammatory, stress, apoptosis and unfolded proteins aggregation. Magnesium Isoglycyrrhizinate (MgIG) has been accepted to be a neuroprotective effect, hepatoprotective and anti-inflammatory molecule. In our vitro researches, MgIG was considered to activate hepatic stellate cells (HSCs) apoptosis by promoting endoplasmic reticulum stress (ERS) detrimental response to a certain extent. Consequently, MgIG showed its potential therapeutic capacity in fibrogenesis and counteracted the pathogenetic aspects, which were involved in integrating current treatments correcting liver fibrosis. In addition, we further verificated the behavior and pathogenic mechanisms in the CCl -induced liver fibrosis in male mice. What surprised us was that with the treatment of MgIG caused the activation of ERS and resisted the activated HSCs in the protective effects on liver damage. We found MgIG significantly promoted the apoptosis of activated HSCs and protected the CCl -induced liver fibrosis. Main molecules came down to the unfolded protein response signaling pathway. Furthermore, MgIG inhibited the levels of the downstream inflammatory cytokines, which were triggered by CCl -induced liver fibrosis. Here, we reported that MgIG improved behavioral impairments induced by intraperitoneal injection of CCl and decreased the expression of proinflammatory factor, which indicated the preserving effects on liver fibrosis. © 2017 BioFactors, 43(6):836-846, 2017.

show abstract

Activation of ERK–p53 and ERK-Mediated Phosphorylation of Bcl-2 Are Involved in Autophagic Cell Death Induced by the c-Met Inhibitor SU11274 in Human Lung Cancer A549 Cells

Cited by 60 publications

References 42 publications

Cyclovirobuxine D Induces Autophagy-Associated Cell Death via the Akt/mTOR Pathway in MCF-7 Human Breast Cancer Cells

Cyclovirobuxine D Induces Autophagy-Associated Cell Death via the Akt/mTOR Pathway in MCF-7 Human Breast Cancer Cells

The potential role of regucalcin in kidney cell regulation: Involvement in renal failure (Review)

Magnesium isoglycyrrhizinate promotes the activated hepatic stellate cells apoptosis via endoplasmic reticulum stress and ameliorates fibrogenesis in vitro and in vivo

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