Growth suppression of a tumorigenic rat liver cell line by the anticancer agent, ET-18-O-CH3, is mediated by inhibition of cytokinesis

Na, Hye-Kyung; Chang, Chia‐Cheng; Trosko, James E.

doi:10.1007/s00280-003-0577-0

Cited by 13 publications

(5 citation statements)

References 29 publications

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“…MCF10A‐ ras cells at 50–60% confluence were inoculated into the plate and exposed to the medium containing chemicals. The cell viability was determined by the trypan blue exclusion method or the conventional MTT reduction assay as described previously [16,33]. All samples were prepared in triplicates.…”

Section: Methodsmentioning

confidence: 99%

“…ET-18-O-CH 3 (edelfosine; 1-O-octadecyl-2-O-methyl-racglycero-3-phosphocholine) is a synthetic analogue of 2-lysophosphatidylcholine that has been found to target cellular membranes and to exert potent anti-neoplastic effects [12,13]. ET-18-O-CH 3 has a broad spectrum of anti-tumorigenic effects [14][15][16][17]. The compound has been known to be a potent inducer of apoptosis in tumor cells, especially in leukemic cells, while sparing normal cells [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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ET‐18‐O‐CH₃‐induced apoptosis is causally linked to COX‐2 upregulation in H‐ras transformed human breast epithelial cells

Inoue

Surh

2005

FEBS Letters

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Abnormally elevated expression of cyclooxygenase-2 (COX-2) has been frequently observed in transformed or malignant cells, and certain non-steroidal anti-inflammatory drugs with COX-2 inhibitory activity exert anti-neoplastic or chemopreventive effects. Contrary to this notion, we have found that a novel alkylphospholipid type antitumor agent ET-18-O-CH 3 (1-Ooctadecyl-2-O-methyl-glycero-3-phosphocholine) induces COX-2 expression in H-ras transformed human breast epithelial cells (MCF10A-ras) while it causes apoptosis at the same concentration range. The addition of a selective COX-2 inhibitor SC-58635 and COX-2 gene knock down with the siRNA blocked ET-18-O-CH 3 -induced apoptosis, suggesting that COX-2 induction by this drug is causally linked to its apoptosis inducing activity. ET-18-O-CH 3 enhanced the transcriptional activities of cyclic AMP response element which is a key regulator of COX-2 expression. 15-Deoxy-D 12,14 prostaglandin J 2 is, an endogenous ligand for peroxisome proliferator-activated receptor c (PPARc), has been known to possess proapoptotic potential in diverse cell types. ET-18-O-CH 3 treatment resulted in elevated release of 15d-PGJ 2 and DNA binding and transcriptional activity of PPARc. Based on these findings, it is likely that ET-18-O-CH 3 induces COX-2 expression and production of 15d-PGJ 2 which may mediate the ET-18-O-CH 3 -induced apoptosis in MCF10A-ras cells.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ET‐18‐O‐CH₃‐induced apoptosis is causally linked to COX‐2 upregulation in H‐ras transformed human breast epithelial cells

Inoue

Surh

2005

FEBS Letters

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“…Likewise, bax -/bak -/double knockout cells are resistant to edelfosine, accumulate in G 2 /M phase following edelfosine treatment, and PC synthesis is weakly and similarly inhibited in either wild-type and bax -/bak -/double knockout cells [24]. In addition, edelfosine arrests cell cycle in G 2 /M phase by inhibiting cytokinesis in a number of cancer cells [86,87] (Gajate, G. and Mollinedo, F., unpublished results). Thus, it is worthy to note that although PC synthesis occurs at the S phase, the whole process of nuclear division is not apparently affected, and only cytokinesis is inhibited in edelfosine-treated cells.…”

Section: Pi-plc Edelfosinementioning

confidence: 99%

Lipid Rafts, Endoplasmic Reticulum and Mitochondria in the Antitumor Action of the Alkylphospholipid Analog Edelfosine

Gajate¹,

Mollinedo

2014

ACAMC

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The so-called alkylphospholipid analogs (APLs) constitute a family of synthetic antitumor compounds that target cell membranes. The ether phospholipid edelfosine has been considered the long-standing prototype of these antitumor agents and promotes apoptosis in tumor cells by a rather selective way, while sparing normal cells. Increasing evidence suggests that edelfosine-induced apoptosis involves a number of subcellular structures in tumor cells, including plasma membrane lipid rafts, endoplasmic reticulum (ER) and mitochondria. Edelfosine has been shown to accumulate in plasma membrane lipid rafts, ER and mitochondria in different tumor cells in a cell type-dependent way. Edelfosine induces apoptosis in several hematopoietic cancer cells by recruiting death receptor and downstream apoptotic signaling molecules into lipid rafts and displacing survival signaling molecules from these membrane domains. However, in vitro and in vivo evidences suggest that edelfosine-induced apoptosis in solid tumor cells is mediated through an ER stress response. Both raft- and ER-mediated proapoptotic responses require a mitochondrial-related step to eventually promote cell death, and overexpression of Bcl-2 or Bcl-xL prevents edelfosine-induced apoptosis. Edelfosine can also interact with mitochondria leading to an increase in mitochondrial membrane permeability and loss of mitochondrial membrane potential. Edelfosine treatment also induced a redistribution of lipid rafts from the plasma membrane to mitochondria, suggesting a raft-mediated link between plasma membrane and mitochondria. The involvement of lipid rafts, ER and mitochondria in the apoptotic response induced by edelfosine may provide new avenues for targeting cancer cells as well as new opportunities for cancer therapy.

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“…1B). PLC activity is required for cytokinesis in both crane fly and Drosophila spermatocytes [Saul et al, 2004, Wong et al, 2005], in sea urchin embryos [Ng et al, 2005] and in mammalian culture cells [Na et al, 2003; Naito et al, 2006]. There is evidence that three PLC isoforms are localized at the cytokinesis furrow in mammalian cells through interactions with PtdIns(4,5) P 2 [Naito et al, 2006].…”

Section: Introductionmentioning

confidence: 99%

Phosphoinositides and cytokinesis: The “PIP” of the iceberg

Échard

2012

Cytoskeleton

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Phosphoinositides[Phosphatidylinositol (PtdIns), phosphatidylinositol 3-monophosphate (PtdIns3P), phosphatidylinositol 4-monophosphate (PtdIns4P), phosphatidylinositol 5-monophosphate (PtdIns5P), phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P 2 ), phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P 2 ), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ), and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P 3 )] are lowly abundant acidic lipids found at the cytosolic leaflet of the plasma membrane and intracellular membranes. Initially discovered as precursors of second messengers in signal transduction, phosphoinositides are now known to directly or indirectly control key cellular functions, such as cell polarity, cell migration, cell survival, cytoskeletal dynamics, and vesicular traffic. Phosphoinositides actually play a central role at the interface between membranes and cytoskeletons and contribute to the identity of the cellular compartments by recruiting specific proteins. Increasing evidence indicates that several phosphoinositides, particularly PtdIns(4,5)P 2 , are essential for cytokinesis, notably after furrow ingression. The present knowledge about the specific phosphoinositides and phosphoinositide modifying-enzymes involved in cytokinesis will be first presented. The review of the current data will then show that furrow stability and cytokinesis abscission require that both phosphoinositide production and hydrolysis are regulated in space and time. Finally, I will further discuss recent mechanistic insights on how phosphoinositides regulate membrane trafficking and cytoskeletal remodeling for successful furrow ingression and intercellular bridge abscission. This will highlight unanticipated connections between cytokinesis and enzymes implicated in human diseases, such as the Lowe syndrome. V C 2012 Wiley Periodicals, Inc

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Growth suppression of a tumorigenic rat liver cell line by the anticancer agent, ET-18-O-CH3, is mediated by inhibition of cytokinesis

Cited by 13 publications

References 29 publications

ET‐18‐O‐CH₃‐induced apoptosis is causally linked to COX‐2 upregulation in H‐ras transformed human breast epithelial cells

ET‐18‐O‐CH₃‐induced apoptosis is causally linked to COX‐2 upregulation in H‐ras transformed human breast epithelial cells

Lipid Rafts, Endoplasmic Reticulum and Mitochondria in the Antitumor Action of the Alkylphospholipid Analog Edelfosine

Phosphoinositides and cytokinesis: The “PIP” of the iceberg

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Growth suppression of a tumorigenic rat liver cell line by the anticancer agent, ET-18-O-CH3, is mediated by inhibition of cytokinesis

Cited by 13 publications

References 29 publications

ET‐18‐O‐CH3‐induced apoptosis is causally linked to COX‐2 upregulation in H‐ras transformed human breast epithelial cells

ET‐18‐O‐CH3‐induced apoptosis is causally linked to COX‐2 upregulation in H‐ras transformed human breast epithelial cells

Lipid Rafts, Endoplasmic Reticulum and Mitochondria in the Antitumor Action of the Alkylphospholipid Analog Edelfosine

Phosphoinositides and cytokinesis: The “PIP” of the iceberg

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ET‐18‐O‐CH₃‐induced apoptosis is causally linked to COX‐2 upregulation in H‐ras transformed human breast epithelial cells

ET‐18‐O‐CH₃‐induced apoptosis is causally linked to COX‐2 upregulation in H‐ras transformed human breast epithelial cells