Abstract
In normal and cancer cells, successful cell division requires accurate duplication of chromosomal DNA. All cells require a multiprotein DNA duplication system (replisomes) for their existence. However, death of normal cells in our body occurs through the apoptotic process. During apoptotic process several crucial genes are downregulated with the upregulation of caspase pathways, leading to ultimate degradation of genomic DNA. In metastatic cancer cells (SKBR-3, MCF -7, and MDA-462), this process is inhibited to achieve immortality as well as overexpression of the enzymes for the synthesis of marker molecules. It is believed that the GSL of the lacto family such as LeX, SA-LeX, LeY, Lea, and Leb are markers on the human colon and breast cancer cells. Recently, we have characterized that a few apoptotic chemicals (cis-platin, L-PPMP, D-PDMP, GD3 ganglioside, GD1b ganglioside, betulinic acid, tamoxifen, and melphalan) in low doses kill metastatic breast cancer cells. The apoptosis-inducing agent (e.g., cis-platin) showed inhibition of DNA polymerase/helicase (part of the replisomes) and also modulated (positively) a few glycolipid-glycosyltransferase (GSL-GLTs) transcriptions in the early stages (within 2 h after treatment) of apoptosis. These Lc-family GSLs are also present on the surfaces of human breast and colon carcinoma cells. It is advantageous to deliver these apoptotic chemicals through the metastatic cell surfaces containing high concentration of marker glycolipids (Lc-GSLs). Targeted application of apoptotic chemicals (in micro scale) to kill the cancer cells would be an ideal way to inhibit the metastatic growth of both breast and colon cancer cells. It was observed in three different breast cancer lines (SKBR-3, MDA-468, and MCF-7) that in 2 h very little apoptotic process had started, but predominant biochemical changes (including inactivation of replisomes) started between 6 and 24 h of the drug treatments. The contents of replisomes (replisomal complexes) during induction of apoptosis are not known. It is known that DNA helicase activities (major proteins catalyze the melting of dsDNA strands) change during apoptotic induction process. Previously DNA Helicase-III was characterized as a component of the replication complexes isolated from carcinoma cells and normal rapid growing embryonic chicken brain cells. Helicase activities were assayed by a novel method (combined immunoprecipitation-ROME assay), and DNA polymerase-alpha activities were determined by regular chain extension of nicked “ACT-DNA,” by determining values obtained from +/− aphidicolin added to the incubation mixtures. Very little is known about the stability of the “replication complexes” (or replisomes) during the apoptotic process. DNA helicases are motor proteins that catalyze the melting of genomic DNA during replication, repair, and recombination processes. In all three breast carcinoma cell lines (SKBR-3, MCF-7, and MDA-468), a common trend, decrease of activities of DNA polymerase-alpha and Helicase-III (estimated and detected with a polyclonal antibody), was observed, after cis-platin- and L-PPMP-induced apoptosis. Previously our laboratory has documented downregulation (within 24–48 h) of several GSL-GLTs with these apoptotic reagents in breast and colon cancer cells also. Perhaps induced apoptosis would improve the prognosis in metastatic breast and colon cancer patients.
[Supported by NIH-NINDS (NS-18005; Jacob Javits Research Grant awards) and NCI (RO1-CA-14764)] to SB and a grant-in-aid from Siemens Corporation to MB.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Agnieszka G, Ewa A, Anna B, Krzyszlof B, Monika C, Elzbieta S (2014) Dinuclear berenil-platinum (II) complexes as modulator of apoptosis in human MCF-7 and MDA-MB231 breast cancer cells. Anti Cancer Agents Med Chem 14(8):1179–1186
Aparicio O, Stout A, Bell S (1999) Differential assembly of Cdc45p and DNA Polymerases at early and late origins of DNA replication. Proc Natl Acad Sci U S A 06(16):9130–9135
Arends MJ, Wyllie AH (1991) Apoptosis: mechanisms and roles in pathology. Int Rev Exp Pathol 32:223–254
Basu S (1991) The serendipity of ganglioside biosynthesis: pathway to CARS and HY-CARS glycosyltransferases. Glycobiology 1:469–475
Basu M, Basu S (1972) Enzymatic synthesis of a tetraglycosylceramide by a galactosyltransferase from rabbit bone marrow. J Biol Chem 247:1489–1495
Basu M, Basu S (1984) Biosynthesis in vitro of Ii-core glycolipids from neolactotetraosylceramide by β1-3 and β1-6 N-acetylglucosaminyltransferases from mouse T-lymphoma. J Biol Chem 259:12557–12562
Basu M, Basu S, Stoffyn A, Stoffyn P (1982) Biosynthesis in vitro of sialyl(α2-3)neolactotetraosylceramide by a sialyltransferase from embryonic chicken brain. J Biol Chem 257:12765–12769
Basu M, De T, Das K, Kyle JW, Chon HC, Schaeper RJ, Basu S (1987) Glycosyltransferases involved in glycolipid biosynthesis. In: Ginsburg V (ed) Methods in enzymology, vol 138. Academic, New York, pp 575–607
Basu M, Hawes JW, Li Z, Ghosh S, Khan FA, Zhang B, Basu S (1991) Biosynthesis in vitro of SA-Lex and SA-diLex by α1-3 fucosyltransferases from colon carcinoma cells and embryonic brain tissues. Glycobiology 1:527–535
Basu S, Basu M, Dastgheib S, Hawes JW (1999) Biosynthesis and regulation of glycosphingolipids. In: Barton D, Nakanishi K, Meth-Cohen O, Pinto BM (eds) Comprehensive natural products chemistry, vol 3. Pergamon Press, New York, pp 107–128
Basu S, Basu M, Das K (2000) Glycosyltransferases in glycosphingolipid biosynthesis. In: Ernst B, Sinay P, Hart G (eds) Oligosaccharides in chemistry and biology – a comprehensive handbook. Wiley-VCH Verlag GmbH, Weinheim
Basu S, Rui M, Mikulla B, Bradley M, Moulton C, Basu M, Banerjee S, Inokuchi JI (2004a) Apoptosis of human carcinoma cells in the presence of inhibitors of Glycosphingolipid biosynthesis: I. Treatment of Colo-205 and SKBR3 cells with isomers of PDMP and PPMP. Glycoconj J 20(3):157–168
Basu S, Rui M, Boyle PJ, Mikulla B, Bradley M, Smith B, Basu M, Banerjee S (2004b) Apoptosis of human carcinoma cells in the presence of potential anti-cancer drugs. III. Treatment of Colo-205 and SKBR-3 cells with cis-platin, Tamoxifen, Melphalan, Betulinic acid, L-PDMP, L-PPMP, and GD3 ganglioside. Glycoconj J 20:563–577
Basu S, Rui M, Basu M, Goodson H, Smith B, Banerjee SV (2004c) Glycosphingolipid metabolism and signaling in apoptotic cancer cells, lipids. In: Haldar D, Das SK (eds) Sphingolipid metabolizing enzymes. Research Signpost, Trivandrum, pp 81–100
Basu S, Rui M, Moskal JR, Basu M, Banerjee S (2012a) Apoptosis of breast cancer cells: XI. Modulation of genes of glycoconjugate biosynthesis and targeted drug delivery. In: Sudhakaran PR, Surolia A (eds) Proceedings of 9th international symposium, biochemical roles of eukaryotic cell surface macromolecules, Advances in experimental medicine and biology, vol 749. Springer, Trivandrum, pp 233–255
Basu S, Rui M, Moskal JR, Basu M (2012b) Ganglioside biosynthesis in developing brains and apoptotic cancer cells. X. Regulation of glyco-genes involved in GD3 and Sialyl-LeX/a syntheses. Neurochem Res 27:1245–1255
Basu S, Rui M, Moskal JR, Basu M (2014) Regulation of glycolipids: XII. Glycosyltransferase 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) Proceedings of 10th international symposium, biochemical roles of eukaryotic cell surface macromolecules, Advances in experimental medicine and biology, vol 842. Springer, Trivandrum, pp 329–354
Basu S, Rui M, Moskal JR, Basu M (2017a) Chapter 4: Biosynthesis of LeX family glycosphingolipids and ifs gene regulation in horizons in cancer research, vol 64 (ed. Watanabe HS). Nova Science Publisher (E-Book), pp 85–100
Basu S, Agarwal A, Basu M, Rui M, Moskal JR (2017b) Protocols of glycosyltransferase assays: gangliosides globoside and Lewis-X intermediate-lactosylceramide biosyntheses in eukaryotic systems. In: Sonnino S, Alessandro (eds) Protocols of gangliosides, Advances in experimental medicine and biology. Springer, New York
Benkovic SJ, Valentine AM, Salinas F (2001) Replisome-mediated DNA replication. Ann Rev Biochem 70:181–208
Bhattacharya P, Basu S (1978) DNA polymerase activities in differentiating mouse neuroblastoma N-18 cells. Proc Natl Acad Sci U S A 75(3):1289–1293
Bhattacharya P, Simet I, Basu S (1979) Inhibition of human neuroblastoma DNA polymerase activities by plant lectins and toxins. Proc Natl Acad Sci U S A 76(5):2218–2221
Bielawski K, Czarnomysy R, Bielawska A, Poplawska B (2013) Cytotoxicity and induction of apoptosis of human breast cancer cells by novel platinum (II) complexes. Environ Toxicol Pharmacol 25(2):254–264
Boehmer PE, Dodson M, Lehman I (1993) The herpes simplex virus type-1 origin binding protein. DNA helicase activity. J Biol Chem 268(2):1220–1225
Bose RN (2002) Biomolecular targets for platinum antitumor drugs. Mini Rev Med Chem 2(2):103–111
Bose RN, Li D, Kennedy M, Basu S (1995) Facile formation of cis-platin Nonapeptide complex of human DNA polymerase-alpha origin. J Chem Soc Commun R Soc Chem 1731–1732
Bose RN, Li D, Yang WW, Basu S (1999) NMR structures of a Nonapeptide from DNA binding domain of human DNA polymerase-alpha determined by iterative complete-relaxation-matrix approach. J Biomol Struct Dyn 16(5):1075–1085
Boyle PJ (2005) Characterization of DNA helicase-III in replication complexes isolated from embryonic chicken brains and breast carcinoma cells. PhD. thesis, University of Notre Dame
Boyle PJ, Campbell BA, Ma R, Moulton C, Tuteja N, Basu S (2003) Differential association of DNA helicase-III in the replisomal complex isolated from developing embryonic chicken brains: as assayed by a new method. FASEB J 17(4):A600
Boyle PJ, Ma R, Tuteja N, Banerjee S, Basu S (2006) Apoptosis of human breast carcinoma cells in the presence of cis-platin and L−/D-PPMP: IV. Modulation of replication complexes and glycolipid: Glycosyltransferases. Glycoconj J 23(3–4):175–187
Budd M, Campbell J (1995) A yeast gene required for DNA replication encodes a protein with homology to DNA helicases. Proc Natl Acad Sci U S A 92(17):7612–7616
Chang LM, Rafter E, Augl C, Bollum FJ (1984) Purification of DNA polymerase-DNA primase complex from calf thymus glands. J Biol Chem 259(23):14679–14687
Costa M, Ochem A, Staub A, Falaschi A (1999) Human DNA helicase VII: a DNA and RNA helicase corresponding to the G3BP protein, an element of the ras transduction pathw2ay. Nucleic Acids Res 27(3):817–821
Crute J, Bruckner R, Dodson M, Lehman I (1991) Herpes simplex-1 helicase-primase. Identification of two nucleoside triphosphatase sites that promotes DNA-helicase action. J Biol Chem 286(31):21252–21256
Enomoto T, Suzuki M, Takahashi M, Kawasaki K, Watanabe Y, Nagata K, Hanaoka F, Yamada M (1985) Purification and characterization of two forms of DNA polymerase-alpha from mouse FM3A cells: DNA polymerase-alpha-primase complex and a free DNA polymerase-alpha. Cell Struct Funct 10:101–107
Gerke V, Creutz CE, Moss SE (2005) Annexin-linking Ca2+ signalling to membrane dynamics. Nat Rev Mel Cell Biol 6(6):449–461
Goetz G, Dean F, Hurwitz J, Matson S (1988) Unwinding of duplex region in DNA by the simian virus 40 large tumor-associated DNA helicase activity. J Biol Chem 263(1):383–392
Ha TK, Kim ME, Yoon JH, Bae SJ, Yoon J, Lee JS (2013) Galagin induces human colon cancer death via the mitochondrial dysfunction and caspase-dependent pathway. Exp Biol Med 238(9):1047–1054
Hanshaw RG, Smith BD (2005) New Reagents for phosphatidylserine recognition and detection of apoptosis. Bioorg Med Chem 13(17):5035–5042
Higashi H, Basu M, Basu S (1985) Biosynthesis in vitro of diasialosyl-neolactotetraosylceramide by a solubilized sialyltransferase from embryonic chicken brain. J Biol Chem 260:824–828
Holmes AM, Cheriathundam E, Bollum FJ, Chang LM (1986) Immunological analysis of the polypeptide structure of calf thymus DNA-polymerase-primase complex. J Biol Chem 261(25):11824–11830
Hotta Y, Stern H (1978) DNA unwinding protein from meiotic cells of Lilium. Biochemistry 17(10):1872–1880
Im DS, Muzyczka N (1992) Partial purification of adeno-associated virus Rep78, Rep52, and Rep40 and their biochemical characterization. J Virol 66(2):1119–1128
Jiang H, Hickey R, Abdel-Aziz W, Tom T, Wills P, Liu J, Malakas L (2002) Human cell DNA replication is mediated by a discrete multiprotein complex. J Cell Biochem 85(4):762–774
Kelley TJ (1993). Subunit structure of DNA polymerase-alpha and its inhibition by antitumor drugs. PhD thesis, Department of Chemistry and Biochemistry, The University of Notre Dame
Kelley TJ, Groll TM, Basu S (1993a) Purification of a galactose binding 56kDa protein from embryonic chicken brain. Its probable role in the initiation of replication. In: Proceedings of Cold Spring Harbor symposium on Euk. DNA Replication September 8–12, 1993, p 75
Kelley TJ, Moghaddas S, Bose R, Basu S (1993b) Inhibition of immunopurified DNA polymerase-alpha from PA-3 prostate tumor cells by platinum (II) antitumor drugs. Cancer Biochem Biophys 13(3):135–146
Kornberg A, Baker TA (1992) DNA replication-2. W.H.Freeman, New York
Koulov AV, Stucker KA, Lakshmi C, Robinson JP, Smith BD (2003) Detection of apoptotic cells using synthetic fluorescent sensor for membrane surfaces that contain phosphatidylserine. Cell Death Differ 10(12):1357–1359
Kroes RA, Panksepp J, Burgdorf J, Otto NJ, Moskal JR (2006) Modeling depression: social-dominance-submission gene expression patterns in rat neocortex. Neuroscience 137(1):47–49
Kunkel TA, Burgers PM (2008) Dividing the workload at a eukaryotic replication fork. Trends Cell Biol 18(11):521–527
Labib K, Torcero J, Diffley J (2000) Uninterrupted MCM2-7 function required for DNA –replication fork progression. Science 286(5471):1643–1647
Letai A (2017) Apoptosis and cancer. Ann Rev Cancer Biol 1:275–294
Lin S, Hickey R, Malakas L (1997) The isolation of DNA synthesome from human leukemia cells. Leuk Res 21:501–512
Lohman TM (1993) Helicase-catalyzed DNA unwinding. J Biol Chem 268(4):2269–2272
Lohman TM, Bjornson KP (1996) Mechanisms of helicase-catalyzed DNA unwinding. Annu Rev Biochem 65:169–214
Maga G, Hubscher U (1996) DNA replication machinery: functional characterization of a complex containing DNA polymerase-alpha, DNA polymerase-delta, and replication factor C suggests an asymmetric DNA polymerase dimer. Biochemistry 35(18):5764–5777
Malkas L, Hickey R, Li C, Pederson N, Baril EA (1990) 21S enzyme complex from HeLa cells that functions in simian virus 40 DNA replication in vitro. Biochemistry 29(27):8362–8374
Matson S, Tabor S, Richardson C (1983) The gene 4 protein of bacteriophage 17. Characterization of helicase activity. J Biol Chem 258(22):14017–14024
McCulloch SD, Kunkel TA (2008) The fidelity of DNA synthesis by eukaryotic replicative and translational synthesis polymerases. Cell Res 18(1):148–161
Mimura S, Masuda T, Matsui T, Takisawa H (2000) Central role for cdc45 in establishing an initiation complex of DNA replication in Xenopus egg extract. Gene Cells 5(6):439–452
Moskal JR, Gardner DA, Basu S (1974) Changes in glycolipid Glycosyl transferases and glutamate decarboxylase and their relationship to differentiation in neuroblastoma cells. Biochem Biophys Res Commun 61:751–758
Peyrone M (1844) Ueber die einwirkung des ammoniaks and platinchlorur. Ann Chem Pharm 51:1–29
Ray S (1988) Studies on DNA replication in vitro by DNA polymerase-alpha/primase complex from embryonic chicken brains. PhD thesis, Department of Chemistry and Biochemistry, University of Notre Dame, Indiana
Ray S, Kelley TJ, Fan L, Basu S (1994) Characterization of DNA polymerase-alpha/primase complex from developing embryonic chicken brains. Indian J Biochem Biophys 3(4):226–235
Rosenberg B, VanCamp L, Krigas T (1965) Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 205:698–699
Rosenberg B, VanCamp L, Trosko JE, Mansour VH (1969) Platinum compounds: a new class of potent antitumor agents. Nature 222(191):385–386
Rossi D, Gaidano G (2003) Messenger of cell death: apoptotic signalling in health and disease. Haematologica 88(2):212–218
Rui M (2008) Apoptosis of breast and colon cancer cells by inhibitors of glycolipid and DNA biosynthesis. PhD thesis, University of Notre Dame, Notre Dame, IN, pp 1–271
Rui M, Koulov A, Moulton C, Basu M, Banerjee S, Goodson H, Basu S (2004) Apoptosis of human breast carcinoma cells in the presence of Disialosyl gangliosides: II. Treatment of SKBR3 cells with GD3 and GD1b gangliosides. Glycoconj J 20(5):319–330
Rui M, Decker NM, Anilus V, Moskal JR, Bergdorf J, Johnson J, Basu M, Banerjee S, Basu S (2009) Post-translational and transcriptional regulation of glycolipid glycosyltransferase genes in apoptotic breast carcinoma cells: VII. After treatment with L-PPMP. Glycoconj J 26:647–661
Rui M, Hopp EA, Decker NM, Loucks A, Johnson JP, Moskal JR, Basu M, Banerjee S, Basu S (2011) VIII. Regulation of glycosyltranferase genes in apoptotic breast cancer cells by inhibitors of glycolipid and DNA biosynthesis in immunology of complex carbohydrates. Adv Exp Med Biol 705:621–642 (editor: Albert Wu)
Seki M, Enomoto T, Eki T, Miyajima A, Murakami Y, Hanaoka F, Ui M (1990) DNA helicase and nucleoside-5′-triphosphatase activities of polyoma virus large antigen. Biochemistry 29(4):1003–1009
Seo YS, Muller F, Lusky M, Gibbs E, Kim H, Phillips B, Hurwitz J, Shlomai J, Kornberg A (1980) A prep riming DNA replication enzyme of Escherichia coli. I. Actions of protein n’: a sequence-specific, DNA dependent ATPase. J Biol Chem 255(14):6794–6798
Seo YS, Mollar F, Lusky M, Gibbs F, Kim H, Phillips B, Hurwitz J (1993) Bovine Papilloma virus (BVPV)-encoded E2 protein enhances binding of E1 protein to the BPV replication origin. Proc Natl Acad Sci U S A 90(7):2865–2869
Shlomai J, Kornberg A (1980) A prepriming DNA replication enzyme of Escherichia coli II. Actions of protein n: a sequence-specific, DNA dependent ATPase. J Biol Chem 255(14):6794–6798
Strasser A, O’Connor L, Dixit VM (2000) Apoptosis signaling. Annu Rev Biochem 69:217–245
Tom T, Malakas L, Hickey R (2002) Identification of multiprotein complexes containing DNA replication factors by native immunoblotting 0f HeLa cell protein preparation with T-antigen-dependent SV-40 replication activity. J Cell Biochem 85(4):762–774
Tuteja N, Tuteja R (2004) Unraveling DNA helicases. Motif structure, mechanism and function. Eur J Biochem 271(10):1849–1863
Tuteja N, Tuteja R, Rehman K, Kang LY, Falaschi A (1990) A DNA helicase from human cells. Nucleic Acids Res 18(23):6785–6802
Tuteja N, Rahman K, Tuteja R, Falaschi A (1991) DNA helicase IV from HeLa cells. Nucleic Acids Res 19(3):3613–3618
Tuteja N, Rahman K, Tuteja R, Ochem A, Slopac D, Falaschi A (1992) DNA helicase-III from HeLa cells: an enzyme that acts preferentially on partially unwound duplexed. Nucleic Acids Res 20(20):5329–5337
Tuteja N, Rahman K, Tuteja R, Falaschi A (1993) Human DNA helicase V. a novel DNA unwinding enzyme from HeLa cells. Nucleic Acid Res 21(10):2323–2329
Tuteja N, Tuteja R, Ochem A, Taneja P, Huang NW, Simonies A, Susic S, Rahman K, Marusic L, Chen J (1994) Human DNA ligase-II: a novel DNA unwinding enzyme identified as the Ku autoantigen. Eur J 13(20):4991–5001
Tuteja N, Cohen A, Tuteja R, Skopac D, Falaschi A (1995) Purification and properties of human DNA helicase-VI. Nucleic Acids Res 23(3):2457–2463
Van Gelder RN, von Zastrow ME, Yool A, Dement WC, Barchas JD, Eherwine JH (1990) Amplified RNA synthesizes from limited quantities of hetero generous cDNA. Proc Natl Acad Sci U S A 87(5):1963–1967
Walter J, Newport J (2000) Initiation of eukaryotic DNA replication: origin unwinding and sequential chromatin association of Cdc45, RPA, and DNA polymerase-alpha. Mol Cell 5(4):617–627
Wilson G, Jindal H, Yeung D, Chen W, Ashwell G (1991) Expression of minute virus of mice major nonstructural protein in insect cells: purification and identification of AYP and helicase activities. Virology 185(1):90–98
Wu Y, Hickey R, Lawlor K, Wills P, Yu F, Ozer H, Starr R, Quant J, Lee M, Malakas LA (1994) A 17S multiprotein form of murine cell DNA polymerase mediates polyoma virus DNAs replication in vitro. J Cell Biochem 54(1):32–46
Wyllie A (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556
Wyllie AH (1987) Apoptosis: cell death in tissue regulation. J Pathol 153:313–316
Yan H, Chen C, Kobayashi R, Newport J (1998) Replication focus-forming activity 1 and the Werner syndrome gene product. Nat Genet 19(4):375–378
Yao NY, O’Donnell M (2009) Replisome structure and conformational dynamics underline fork progression past obstacles. Curr Opin Cell Biol 21:336–343
Yao NY, O’Donnell M (2010) The replisome (a review). Cell 141(6):1088–1092
Yao NY, O’Donnell M (2016) DNA replication machines. Clin Rev Biochem Mol Biol 51:135–149
Yao NY, O’Donnell ME (2017) DNA replication: how does a sliding clamp slide? Curr Biol 27(4):R174–R176
Zou J, Stillman B (2000) Assembly of a complex containing Cdc45p, replication protein A, and Mcm2p of replication origins controlled by S-phase cyclin dependent kinases and Cdc7p-Dbf4p kinase. Mol Cell Biol 20(9):3086–3096
Zyskind L, Smith D (1977) E coli dnaB mutant: direct involvement of the dnaB252 gene product in the synthesis of an origin-ribonucleic acid species during initiation of a round of deoxyribonucleic replication. J Bacteriol 129(3):1476–1486
Acknowledgment
We thank Mrs. Dorisanne Nielsen and Mr. Eric Kuehner for their help during the preparation of this manuscript. We thank coworkers of Dr. Narendra Tuteja for supplying us mono- and polyclonal antibodies against DNA Helicase-III, coworkers of Dr. Sipra Banerjee for supplying us all three (SKBR-3, MCF-7, and MDA-468) human breast carcinoma cells, and coworkers of Professor Joseph R. Moskal for teaching our students in detail about the DNA microarray experiments.
The Jacob Javits Research Award from NIH-NINDS NS-18005, Coleman Cancer Foundation, and NCI grant-CA-14764 to S. Basu and a grant-in-aid from Siemens Corporation to M. Basu supported this work.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Basu, S.C. et al. (2018). Induction of Apoptosis in Metastatic Breast Cancer Cells: XV. Downregulation of DNA Polymerase-α – Helicase Complex (Replisomes) and Glyco-Genes. In: Chattopadhyay, K., Basu, S. (eds) Biochemical and Biophysical Roles of Cell Surface Molecules. Advances in Experimental Medicine and Biology, vol 1112. Springer, Singapore. https://doi.org/10.1007/978-981-13-3065-0_15
Download citation
DOI: https://doi.org/10.1007/978-981-13-3065-0_15
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-3064-3
Online ISBN: 978-981-13-3065-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)