TY - JOUR
T1 - Ganglioside biosynthesis in developing brains and apoptotic cancer cells
T2 - X. regulation of glyco-genes involved in GD3 and Sialyl-Lex/a syntheses
AU - Basu, Subhash
AU - Ma, Rui
AU - Moskal, Joseph R.
AU - Basu, Manju
N1 - Funding Information:
Acknowledgments The authors greatly acknowledge the help of Mrs. Dorisanne Nielsen and Mr. Eric Kuehner during preparation of this manuscript. Our work on Regulation of glycosphingolipid in apoptotic carcinoma cells was supported by grants from NIH: NS-18005 (Jacob Javits Award) and from NCI: CA-14764.
PY - 2012/6
Y1 - 2012/6
N2 - Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid are ubiquitous in the central nervous system. At least six DSL-glycosyltransferase activities (GLTs Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid (or NAc-Neuraminic acid) are ubiquitous in the central nervous system. At least six GSL-glycosyltransferase activities (GLTs) of Basu-Roseman pathway catalyzing the biosynthesis of these gangliosides have been characterized in developing chicken brains. Most of these glyco-genes are expressed in the early stages (7-17 days) of brain development and lowered in the adult stage, but the cause of reduction of enzymatic activities of these GLTs in the adult stages is not known. In order to study glyco-gene regulation we used four clonal metastatic cancer cells of colon and breast cancer tissue origin (Colo-205, SKBR-3, MDA-468, and MCF-3). The glyco-genes for synthesis of SA-LeX and SA-LeA (which contain N-acetylglucosamine, sialic acid and fucose) in these cells were modulated differently at different phases (between 2 and 48 h) of apoptotic inductions. L-PPMP, D-PDMP (inhibitor of glucosylceramide biosynthesis), Betulinic Acid (a triterpinoid isolated from bark of certain trees and used for cancer treatment in China), Tamoxifen a drug in use in the west for treatment of early stages of the disease in breast cancer patients), and cis-platin (an inhibitor of DNA biosynthesis used for testicular cancer patients) were used for induction of apoptosis in the abovementioned cell lines. Within 2-6 h, transcriptional modulation of a number of glyco-genes was observed by DNAmicro-array (containing over 300 glyco genes attached to the glass cover slips) studies. Under long incubation time (24-48 h) almost all of the glyco-genes were downregulated. The cause of these glyco-gene regulations during apoptotic induction in metastatic carcinoma cells is unknown and needs future investigations for further explanations. These apoptotic agents could be employed as a new generation of anti-cancer drugs after properly delivered to the patients.
AB - Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid are ubiquitous in the central nervous system. At least six DSL-glycosyltransferase activities (GLTs Gangliosides, the acidic glycosphingolipids (GSLs) containing N-acetylgalactosamine and sialic acid (or NAc-Neuraminic acid) are ubiquitous in the central nervous system. At least six GSL-glycosyltransferase activities (GLTs) of Basu-Roseman pathway catalyzing the biosynthesis of these gangliosides have been characterized in developing chicken brains. Most of these glyco-genes are expressed in the early stages (7-17 days) of brain development and lowered in the adult stage, but the cause of reduction of enzymatic activities of these GLTs in the adult stages is not known. In order to study glyco-gene regulation we used four clonal metastatic cancer cells of colon and breast cancer tissue origin (Colo-205, SKBR-3, MDA-468, and MCF-3). The glyco-genes for synthesis of SA-LeX and SA-LeA (which contain N-acetylglucosamine, sialic acid and fucose) in these cells were modulated differently at different phases (between 2 and 48 h) of apoptotic inductions. L-PPMP, D-PDMP (inhibitor of glucosylceramide biosynthesis), Betulinic Acid (a triterpinoid isolated from bark of certain trees and used for cancer treatment in China), Tamoxifen a drug in use in the west for treatment of early stages of the disease in breast cancer patients), and cis-platin (an inhibitor of DNA biosynthesis used for testicular cancer patients) were used for induction of apoptosis in the abovementioned cell lines. Within 2-6 h, transcriptional modulation of a number of glyco-genes was observed by DNAmicro-array (containing over 300 glyco genes attached to the glass cover slips) studies. Under long incubation time (24-48 h) almost all of the glyco-genes were downregulated. The cause of these glyco-gene regulations during apoptotic induction in metastatic carcinoma cells is unknown and needs future investigations for further explanations. These apoptotic agents could be employed as a new generation of anti-cancer drugs after properly delivered to the patients.
KW - Apoptosis
KW - Breast cancer cells
KW - GD3
KW - Ganglioside biosynthesis
KW - Glyco-gene regulation
KW - SA-Lex
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UR - http://www.scopus.com/inward/citedby.url?scp=84862901145&partnerID=8YFLogxK
U2 - 10.1007/s11064-012-0762-9
DO - 10.1007/s11064-012-0762-9
M3 - Review article
C2 - 22488330
AN - SCOPUS:84862901145
SN - 0364-3190
VL - 37
SP - 1245
EP - 1255
JO - Neurochemical Research
JF - Neurochemical Research
IS - 6
ER -
