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Int. J. Mol. Sci. 2016, 17(5), 652; doi:10.3390/ijms17050652

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

Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, SungKyunKwan University, 300 Chunchun-Dong, Jangan-Gu, Suwon City, Kyunggi-Do 440-746, Korea
Research Institute, Davinch-K Co., Ltd., B1603-3, 606, Seobusaet-gil, Geumcheon-gu, Seoul 153-719, Korea
Division of Enteric Diseases, Center for Infectious Diseases Research, Korea National Institute of Health, Heungdeok-gu, Cheongju 363-951, Korea
Functional Genomics Laboratory, Department of Animal Sciences, the Ohio State University, 2029 Fyffe Court, Columbus, OH 43210, USA
Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Korea
Faculty of Medicinal Biotechnology, Dong-A University, Busan 604-714, Korea
Division of Applied Medicine, School of Korean Medicine, Pusan National University, Yangsan City, Gyeongsangnam-Do 626-870, Korea
College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea
Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Seoul 06351, Korea
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Ester Boix
Received: 22 March 2016 / Revised: 13 April 2016 / Accepted: 21 April 2016 / Published: 30 April 2016
(This article belongs to the Special Issue Glycan–Receptor Interaction)
View Full-Text   |   Download PDF [3184 KB, uploaded 30 April 2016]   |  


Gangliosides have been known to play a role in the regulation of apoptosis in cancer cells. This study has employed disialyl-ganglioside GD1b to apoptosis in human breast cancer MCF-7 cells using exogenous treatment of the cells with GD1b and endogenous expression of GD1b in MCF-7 cells. First, apoptosis in MCF-7 cells was observed after treatment of GD1b. Treatment of MCF-7 cells with GD1b reduced cell growth rates in a dose and time dependent manner during GD1b treatment, as determined by XTT assay. Among the various gangliosides, GD1b specifically induced apoptosis of the MCF-7 cells. Flow cytometry and immunofluorescence assays showed that GD1b specifically induces apoptosis in the MCF-7 cells with Annexin V binding for apoptotic actions in early stage and propidium iodide (PI) staining the nucleus of the MCF-7 cells. Treatment of MCF-7 cells with GD1b activated apoptotic molecules such as processed forms of caspase-8, -7 and PARP (Poly(ADP-ribose) polymerase), without any change in the expression of mitochondria-mediated apoptosis molecules such as Bax and Bcl-2. Second, to investigate the effect of endogenously produced GD1b on the regulation of cell function, UDP-gal: β1,3-galactosyltransferase-2 (GD1b synthase, Gal-T2) gene has been transfected into the MCF-7 cells. Using the GD1b synthase-transfectants, apoptosis-related signal proteins linked to phenotype changes were examined. Similar to the exogenous GD1b treatment, the cell growth of the GD1b synthase gene-transfectants was significantly suppressed compared with the vector-transfectant cell lines and transfection activated the apoptotic molecules such as processed forms of caspase-8, -7 and PARP, but not the levels of expression of Bax and Bcl-2. GD1b-induced apoptosis was blocked by caspase inhibitor, Z-VAD. Therefore, taken together, it was concluded that GD1b could play an important role in the regulation of breast cancer apoptosis. View Full-Text
Keywords: disialyl-ganglioside GD1b; human breast cancer MCF-7 cells; apoptosis; caspase; human β1,3-galactosyltransferase-2 (GD1b synthase; Gal-T2) disialyl-ganglioside GD1b; human breast cancer MCF-7 cells; apoptosis; caspase; human β1,3-galactosyltransferase-2 (GD1b synthase; Gal-T2)

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Ha, S.-H.; Lee, J.-M.; Kwon, K.-M.; Kwak, C.-H.; Abekura, F.; Park, J.-Y.; Cho, S.-H.; Lee, K.; Chang, Y.-C.; Lee, Y.-C.; Choi, H.-J.; Chung, T.-W.; Ha, K.-T.; Chang, H.-W.; Kim, C.-H. Exogenous and Endogeneous Disialosyl Ganglioside GD1b Induces Apoptosis of MCF-7 Human Breast Cancer Cells. Int. J. Mol. Sci. 2016, 17, 652.

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