RNA-Dependent Protein Kinase Is Essential for 2-Methoxyestradiol-Induced Autophagy in Osteosarcoma Cells

Yang, Cheng-Ao; Shogren, Kristen L.; Goyal, Ribu; Bravo, Dalibel; Yaszemski, Michael J.; Maran, Avudaiappan

doi:10.1371/journal.pone.0059406

Cited by 23 publications

(20 citation statements)

References 43 publications

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“…The bisindolic alkaloid voacamine (VOA), isolated from the plant Peschiera fuchsiaefolia, is an autophagy inducer that can exert an apoptosis-independent cytotoxic effect on both wild-type and MDR tumor cells by promoting LC3 expression and conversion [100]. The 2-Methoxyestradiol (2-ME) treatment was correlated with the formation of autophagosomes in human osteosarcoma cells by inducing the conversion of microtubule-associated protein LC3-I to LC3-II, requiring ATG7 expression [101]. Moreover, autophagy could play an important role in 2-ME-mediated anti-tumor actions in osteosarcoma.…”

Section: Programmed Cell Death In the Treatment Of Osteosarcomamentioning

confidence: 99%

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

Yang

et al. 2016

Oncotarget

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Osteosarcoma is the most common primary bone tumor in children and adolescents. Although combined therapy including surgery and multi-agent chemotherapy have resulted in great improvements in the overall survival of patients, chemoresistance remains an obstacle for the treatment of osteosarcoma. Molecular targets or effective agents that are actively involved in cell death including apoptosis, autophagy and necroptosis have been studied. We summarized how these agents (novel compounds, miRNAs, or proteins) regulate apoptotic, autophagic and necroptotic pathways; and discussed the current knowledge on the role of these new agents in chemotherapy resistance in osteosarcoma.

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Section: Programmed Cell Death In the Treatment Of Osteosarcomamentioning

confidence: 99%

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

Yang

et al. 2016

Oncotarget

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“…27,28 A cell autophagic response to NP exposure will result in the activation of lysosomal proteases and an increase in the expression of the autophagic marker LC3I/II. 29 A weak increase of the expression of the lysosomal protease procathepsin D and cathepsin D was observed in CaCo 2 cells exposed to NS-USPIO NPs, but not to OA-USPIO NPs, suggesting that the level of intracellular iron is responsible for the cathepsin D as well as CD71 responses. We have previously shown in human endothelial cells an autophagic response to the highly internalized cationic amino-PVA-USPIO NPs.…”

Section: Discussionmentioning

confidence: 91%

Differential stress reaction of human colon cells to oleic-acid-stabilized and unstabilized ultrasmall iron oxide nanoparticles

Schütz¹,

Staedler²,

Crosbie-Staunton³

et al. 2014

IJN

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Therapeutic engineered nanoparticles (NPs), including ultrasmall superparamagnetic iron oxide (USPIO) NPs, may accumulate in the lower digestive tract following ingestion or injection. In order to evaluate the reaction of human colon cells to USPIO NPs, the effects of non-stabilized USPIO NPs (NS-USPIO NPs), oleic-acid-stabilized USPIO NPs (OA-USPIO NPs), and free oleic acid (OA) were compared in human HT29 and CaCo 2 colon epithelial cancer cells. First the biophysical characteristics of NS-USPIO NPs and OA-USPIO NPs in water, in cell culture medium supplemented with fetal calf serum, and in cell culture medium preconditioned by HT29 and CaCo 2 cells were determined. Then, stress responses of the cells were evaluated following exposure to NS-USPIO NPs, OA-USPIO NPs, and free OA. No modification of the cytoskeletal actin network was observed. Cell response to stress, including markers of apoptosis and DNA repair, oxidative stress and degradative/autophagic stress, induction of heat shock protein, or lipid metabolism was determined in cells exposed to the two NPs. Induction of an autophagic response was observed in the two cell lines for both NPs but not free OA, while the other stress responses were cell- and NP-specific. The formation of lipid vacuoles/droplets was demonstrated in HT29 and CaCo 2 cells exposed to OA-USPIO NPs but not to NS-USPIO NPs, and to a much lower level in cells exposed to equimolar concentrations of free OA. Therefore, the induction of lipid vacuoles in colon cells exposed to OA utilized as a stabilizer for USPIO NPs is higly amplified compared to free OA, and is not observed in the absence of this lipid in NS-USPIO NPs.

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“…Autophagy is a homeostatic mechanism through which cellular proteins and organelles are enveloped in autophagosomes and subjected to lysosomal degradation and recycling. We have previously demonstrated that 2‐ME induces autophagy in osteosarcoma cells but not in normal osteoblasts [Yang et al, ]. Autophagy in cancer has been widely investigated and shown to have a dual role by contributing to either cell survival or as step to cell death.…”

Section: Discussionmentioning

confidence: 99%

“…2-ME has been implicated in the regulation of many signaling pathways [Mukhopadhyay and Roth, 1997;Seegers et al, 1997;Schumacher et al, 1999;LaVallee et al, 2003;Wimbauer et al, 2012]. 2-ME has been shown to induce cell death and autophagy in osteosarcoma cells, but not in normal osteoblasts [Shogren et al, 2007;Maran et al, 2008;Wimbauer et al, 2012;Yang et al, 2013]. Since the Wnt antagonist Frzb protein has been shown to have a tumor suppressive role in osteosarcoma [Mandal et al, 2007], in this report, we have investigated whether 2-ME-mediated anti-tumor effects in osteosarcoma cells involve the Frzb protein.…”

mentioning

confidence: 99%

2‐Methoxyestradiol‐Mediated Induction of Frzb Contributes to Cell Death and Autophagy in MG63 Osteosarcoma Cells

Bravo

Shogren

Zuo

et al. 2017

J of Cellular Biochemistry

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Osteosarcoma is a bone tumor that mainly affects children and adolescents. Although its pathogenesis is still not fully understood, activation of Wnt signaling has been implicated in the development and metastasis of osteosarcoma. In this report, we have investigated the effect of the anti-tumor compound, 2-methoxyestradiol (2-ME) on Wnt antagonist frizzled-related protein b (Frzb), also known as secreted frizzled-related protein (sFRP)3 in human osteosarcoma (MG63) cells. Our results show that 2-ME treatment induces Frzb gene promoter activity, and increases Frzb mRNA and protein levels in osteosarcoma cells. In addition, 2-ME treatment regulates downstream Wnt signaling, increasing the cytoplasmic levels of β-catenin, and blocking β-catenin-mediated Wnt activation in osteosarcoma cells. 2-ME-mediated induction of Frzb protein expression is specific to osteosarcoma cells, as it does not affect Frzb expression in normal primary human osteoblasts. Furthermore, 2-ME-induced apoptosis and autophagy are blocked in osteosarcoma cells transfected with Frzb siRNAs. Taken together, these studies demonstrate that Frzb protein plays an important role in 2-ME-mediated anti-tumor mechanisms in osteosarcoma cells. J. Cell. Biochem. 118: 1497-1504, 2017. © 2016 Wiley Periodicals, Inc.

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RNA-Dependent Protein Kinase Is Essential for 2-Methoxyestradiol-Induced Autophagy in Osteosarcoma Cells

Cited by 23 publications

References 43 publications

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

Differential stress reaction of human colon cells to oleic-acid-stabilized and unstabilized ultrasmall iron oxide nanoparticles

2‐Methoxyestradiol‐Mediated Induction of Frzb Contributes to Cell Death and Autophagy in MG63 Osteosarcoma Cells

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