Exogenous and Endogeneous Disialosyl Ganglioside GD1b Induces Apoptosis of MCF-7 Human Breast Cancer Cells

Ha, Sun-Hyung; Lee, Ji-Min; Kwon, Kyung-Min; Kwak, Choong Hwan; Abekura, Fukushi; Park, Jun-Young; Cho, Seung-Hak; Lee, Kichoon; Chang, Young‐Chae; Lee, Young Choon; Choi, Hee‐Jung; Chung, Tae‐Wook; Ha, Ki‐Tae; Chang, Hyeun‐Wook; Kim, Cheorl-Ho

doi:10.3390/ijms17050652

Cited by 19 publications

(18 citation statements)

References 47 publications

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“…4). In contrast, the ER positive (+) MCF-7 cells (ER+) 2 showed the increased expression level of ICAM-1. This clearly suggested that the estrogen receptor is indeed a co-regulator to regulate the ICAM-1 expression with GD3 to GD2 conversion in human breast cancer cells.…”

Section: Discussionmentioning

confidence: 92%

“…3A, B, C, D, E), suggesting that over-expression of GD3 synthase suppresses invasion activity by down-regulation of ICAM-1. Interestingly, when SK-BR3 cells were used as another type of ER negative human breast cancer cell line, the SK-BR3 (ER-) cells exhibited the reduced level of ICAM-1 expression likely to MDA-MB231 cells, which are also ER negative breast cancer cells 2 (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

“…The human breast cancer cell lines of ER positive MCF-7 (ER+), ER negative SK-BR3 (ER-) and ER negative MDA-MB231 (ER-) cells 2, 23 were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% or 5% fetal bovine serum respectively. To construct the GD3 synthase expressing plasmid, a 1026 bp DNA fragment including the human GD3 synthase coding region was amplified by PCR using the primers sense (5´- GATATC GCCGCCACCATGGCTGTACTGGCGTGGAAG-3´) and antisense (5´- CTCGAG CTAGGAAGTGGGCTGGAGTGA-3´), and human melanoma cDNA as template.…”

Section: Methodsmentioning

confidence: 99%

“…Gangliosides are sialylated glycosphingolipids which are ubiquitously expressed in mammalian plasma membranes and they play crucial roles in cellular interaction, adhesion, differentiation and apoptosis 1, 2. To synthesize gangliosides in cells, lactosyl ceramide (Lac-Cer) is processed by different pathways composed of various glycosyltransferases or sialyltranferases 1, 3.…”

Section: Introductionmentioning

confidence: 99%

“…It has also been reported that antibodies against GD2 inhibits proliferative phenotype of tumor cells, triggering apoptotic cell death in small cell lung cancer cell lines (SCLC) 11. Recently, our group reported that the apoptotic functions of disialyl GD1b in human breast cancer MCF-7 cells 2, where endogenous and exogenous GD1b effectively promoted apoptotic cell death in human breast carcinoma SKBR3 cells.…”

Section: Introductionmentioning

confidence: 99%

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Disialyl GD2 ganglioside suppresses ICAM-1-mediated invasiveness in human breast cancer MDA-MB231 cells

Kwon¹,

Chung²,

Kwak³

et al. 2017

Int. J. Biol. Sci.

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The disialoganglioside GD3 has been considered to be involved in tumor progression or suppression in various tumor cells. However, the significance of the biological functions of GD3 in breast cancer cells is still controversial. This prompted us to study the possible relationship(s) between GD3 expression and the metastatic potential of a breast cancer MDA-MB231 cells as an estrogen receptor negative (ER-) type. The human GD3 synthase cDNA was transfected into MDA-MB231 cells, and G-418 bulk selection was used to select cells stably overexpressing the GD3 synthase. In vitro invasion potentials of the GD3 synthase over-expressing cells (pc3-GD3s) were significantly suppressed when compared with control cells. Expression of intercellular adhesion molecule-1 (ICAM-1; CD54) was down-regulated in the pc3-GD3s cells and the decrease in ICAM-I expression is directly related to the decrease in invasiveness of the pc3-GD3s cells. Another type of ER negative SK-BR3 cells exhibited the similar level of ICAM-1 expression as MDA-MB231 cells, while the ER positive MCF-7 cells (ER+) showed the increased expression level of ICAM-1. Then, we investigated signaling pathways known to control ICAM-1 expression. No difference was observed in the phosphorylation of ERK and p38 between the pc3-GD3s and control cells (pc3), but the activation of AKT was inhibited in pc3-GD3s, and not in the control (pc3). In addition, the composition of total gangliosides was changed between control (pc3) and pc3-GD3s cells, as confirmed by HPTLC. The pc3-GD3s cells had an accumulation of the GD2 instead of the GD3. RT-PCR results showed that not only GD3 synthase, but also GM2/GD2 synthase (β4-GalNc T) expression was increased in pc3-GD3s cells. Overexpression of GD3 synthase suppresses the invasive potential of human breast cancer MDA-MB-231 cells through down-regulation of ICAM-1 and the crucial pathway to allow the apoptotic effect has been attributed to accumulation of the GD2 ganglioside. ER has been linked to the ICAM-1 expression with GD3 to GD2 conversion in human breast cancer cells. This is the first finding of the endogenous sialyltransferase functions in tumor cells.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Disialyl GD2 ganglioside suppresses ICAM-1-mediated invasiveness in human breast cancer MDA-MB231 cells

Kwon¹,

Chung²,

Kwak³

et al. 2017

Int. J. Biol. Sci.

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Conformational Transition‐Triggered Disassembly of Therapeutic Peptide Nanomedicine for Tumor Therapy

Wang

Yang

Hou

et al. 2021

Adv Healthcare Materials

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Cationic therapeutic peptides have received widespread attention due to their excellent antibacterial and antitumor properties. However, most of these peptides have undesirable delivery efficiency and high hemolytic toxicity due to the positively charged α‐helix structure containing many lysine and arginine, which may restrict its in vivo applications. Herein, a conformationally transformed therapeutic peptide Pep‐HCO3 modified with bicarbonates on guanidine groups is designed. Such a design allows Pep‐HCO3 ((nap‐RAGLQFPVGRLLRRLLRRLLR) nHCO3) to self‐assemble into nanoparticles (NP‐Pep) due to disrupting helix folding and the formation of intermolecular hydrogen bonding between bicarbonates and guanidine groups. When pH is from 7.4 to 6.5 at the tumor sites, guanidine bicarbonate can be hydrolyzed to form CO2 and guanidine groups, resulting in the disassembling of the NP‐Pep into monomers α‐Pep with a positively charged α‐helix structure. In vivo, NP‐Pep not only inhibits the tumor growth of xenografted mice with a twofold enhanced inhibition rate compared with α‐Pep treatment group, but also significantly reduces the hemolytic toxicity by responding to the pH of tumor microenvironment. Therefore, the strategy of conformational transition‐triggered disassembly of nanoparticles allows efficient delivery of cationic therapeutic peptides and lowering the hemolytic toxicity, which may provide an avenue for developing high‐performance cationic peptide in vivo applications.

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Monosialyl Ganglioside GM3 Decreases Apolipoprotein B-100 Secretion in Liver Cells

et al. 2017

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Some sialic acid-containing glycolipids are known to regulate development of atherosclerosis with accumulated plasma apolipoprotein B-100 (Apo-B)-containing lipoproteins, because Apo-B as an atherogenic apolipoprotein is assembled mainly in VLDL and LDL. Previously, we have elucidated that disialyl GD3 promotes the microsomal triglyceride transfer protein (MTP) gene expression and secretion of triglyceride (TG)-assembled ApoB, claiming the GD3 role in ApoB lipoprotein secretion in liver cells. In the synthetic pathway of gangliosides, GD3 is synthesized by addition of a sialic acid residue to GM3. Thus, there should be some regulatory links between GM3 and GD3. In this study, exogenous and endogenous monosialyl GM3 has been examined how GM3 plays a role in ApoB secretion in Chang liver cells in a view point of MTP and ApoB degradation in the same cells. The level of GM3 ganglioside in the GM3 synthase gene-transfected cells was increased in the cell extract, but not in the medium. In addition, GM3 synthase gene-transfected cells showed a diminished secretion of TG-enriched ApoB with a lower content of TG in the medium. Exogenous GM3 treatment for 24 h exerted a dose dependent inhibitory effect on ApoB secretion together with TG, while a liver-specific albumin was unchanged, indicating that GM3 effect is limited to ApoB secretion. GM3 decreased the mRNA level of MTP gene, too. ApoB protein assembly dysregulated by GM3 indicates the impaired ApoB secretion is caused by a proteasome-dependent pathway. Treatment with small interfering RNAs (siRNAs) decreased ApoB secretion, but GM3-specific antibody did not. These results indicate that plasma membrane associated GM3 inhibits ApoB secretion, lowers development of atherosclerosis by decreasing the secretion of TG-enriched ApoB containing lipoproteins, suggesting that GM3 is an inhibitor of ApoB and TG secretion in liver cells. J. Cell. Biochem. 118: 2168-2181, 2017. © 2017 Wiley Periodicals, Inc.

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Exogenous and Endogeneous Disialosyl Ganglioside GD1b Induces Apoptosis of MCF-7 Human Breast Cancer Cells

Cited by 19 publications

References 47 publications

Disialyl GD2 ganglioside suppresses ICAM-1-mediated invasiveness in human breast cancer MDA-MB231 cells

Disialyl GD2 ganglioside suppresses ICAM-1-mediated invasiveness in human breast cancer MDA-MB231 cells

Conformational Transition‐Triggered Disassembly of Therapeutic Peptide Nanomedicine for Tumor Therapy

Monosialyl Ganglioside GM3 Decreases Apolipoprotein B-100 Secretion in Liver Cells

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