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Regulations of Glycolipid: XI. Glycosyltransferase (GSL: GLTs) Genes Involved in SA-LeX and Related GSLs Biosynthesis in Carcinoma Cells by Biosimilar Apoptotic Agents: Potential Anticancer Drugs

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Biochemical Roles of Eukaryotic Cell Surface Macromolecules

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 842))

Abstract

New biosimilar apoptotic agents identified during our recent studies can be employed as a new generation of anti-cancer drugs after being properly delivered to the patients by a proper drug delivery system. These agents regulate at gene level as evidenced by both translational and transcriptional studies. 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-7). The glyco-genes for synthesis of SA-Lex and SA-Lea (which contain N-acetylglucosamine, sialic acid, and fucose) in these cells was modulated differentially at various phases induced by l-PPMP, d-PDMP (inhibitor of glucosylceramide biosynthesis), Betulinic Acid (a triterpinoid isolated from the 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) when used for induction of apoptosis in the above mentioned cell lines. Biosimilarities of these chemicals reside in their killing abilities of these highly metastatic cells by apoptosis. Within 2–6 h, transcriptional modulation of a number of glyco-genes was observed by DNA micro-array (containing over 340 glyco-genes attached to the glass cover slips) studies. Under a long incubation time (24–48 h) almost all of the glyco-gene products, glycolipid: glycosyltransferases (GLTs) 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. At least two GSL-GLT activities (GLTs) of Basu-Roseman pathway2 catalyzing the biosynthesis of GD1a and GD3 gangliosides and more than five GSL: GLTs in the SA-LeX pathway2 have been regulated. Most of these glyco-genes are expressed in the early stages (7–17 days) of embryonic chicken-brain development and lowered in the adult stage. However, the mechanism of regulation of the enzymatic activities of these GLTs in the synthesis of SA-LeX (human cancer cell marker) is unknown. Our recent attempt of in vitro Glyco-gene regulation in apoptotic metastatic cells may lead us to explain the in vivo Glyco-gene regulation in normal or diseased animal organs.

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Acknowledgments

We thank Mrs. Dorisanne Nielsen and Mr. Eric Kuehner for their help during preparation of this manuscript. Our sincere thanks to Dr. Sipra Banerjee of the Cleveland Clinic Foundation who initially (decade ago) provided us the clones of the breast carcinoma cell: SKBR-3, MDA-468, and MCF-7, which we have maintained continuously for this work. This research work was supported by the Jacob Javits Research Award from NIH-NINDS, NCI, and the Coleman Cancer Foundation (continuous long-term support) to S. Basu; and a grant-in-aid from Siemens Corporation to M. Basu.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry and Cancer Drug Delivery Research Foundation, University of Notre Dame, Notre Dame, IN, 46556, USA

    Subhash Basu & Manju Basu

  2. Diagnostic Division, Siemens Corporation, Shanghai, China

    Rui Ma

  3. The Falk Center for Molecular Therapeutics, Northwestern University, Evanston, IL, 60201, USA

    Joseph R. Moskal

Authors
  1. Subhash Basu
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  2. Rui Ma
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  3. Joseph R. Moskal
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  4. Manju Basu
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Corresponding author

Correspondence to Subhash Basu .

Editor information

Editors and Affiliations

  1. Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, India

    Abhijit Chakrabarti

  2. Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, India

    Avadhesha Surolia

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© 2015 Springer International Publishing Switzerland

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Basu, S., Ma, R., Moskal, J.R., Basu, M. (2015). Regulations of Glycolipid: XI. Glycosyltransferase (GSL: GLTs) Genes Involved in SA-LeX and Related GSLs Biosynthesis in Carcinoma Cells by Biosimilar Apoptotic Agents: Potential Anticancer Drugs. In: Chakrabarti, A., Surolia, A. (eds) Biochemical Roles of Eukaryotic Cell Surface Macromolecules. Advances in Experimental Medicine and Biology, vol 842. Springer, Cham. https://doi.org/10.1007/978-3-319-11280-0_21

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