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A Kinetic Assay for Drug Discovery: Part 2, Sodium Sulfate

Received: 31 March 2020     Accepted: 17 April 2020     Published: 30 April 2020
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Abstract

Clumped cells are generally more dangerous than single cells in cancer spread, thrombocytosis and biofilm infectivity. Here a simple direct kinetic assay is used to examine a specific reagent for anti-clumping activity using a Prefer fixed yeast (Saccharomyces cerevisiae) model that has been recently described by us in detail using other reagents. In 1212 trials by 17 investigators sodium sulfate (1-3 mg per ml deionized water) was examined by measuring percentage single cells, number of clumps and number of cells per clump over a 60 min time course, with standard deviations and t-tests to determine any significant differences between controls and experimentals. Sodium sulfate showed sometimes inconsistent unclumping activity especially in magnitude of effects. When percentage of single cells increased, clump number and/or number of cells per clump generally decreased, helping to validate the assay. An example of these findings in 60 trials at 60 min with 1-3 mg sodium sulfate per ml deionized water: 1 mg 15% increased singles (p<0.01), 29% decreased clumps (p<0.01), 11% decreased cells per clump (p>0.05); 2 mg 12% increased singles (p<0.01), 20% decreased clumps (p<0.01), 30% decreased cells per clump (p<0.01); 3 mg 27% increased singles (p<0.01), 36% decreased clumps (p<0.01), 28% decreased cells per clump (p<0.02). Here sodium sulfate showed promise as an anti-cell-clumping reagent together with sodium citrate reported previously in part 1 of this study. Sodium citrate is a known human anticoagulant independently identified with this assay, helping to validate the assay for drug discovery applications.

Published in American Journal of Applied Scientific Research (Volume 6, Issue 2)
DOI 10.11648/j.ajasr.20200602.12
Page(s) 39-42
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2020. Published by Science Publishing Group

Keywords

Sodium Sulfate Unclumps Cells, Fixed Yeast Model, Kinetic Assay, Drug Discovery

References
[1] F. Castro-Giner, N. Aceto Tracking cancer progression: from circulating tumor cells to metastasis Genome Med, 12 (2020) pp. 31-57.
[2] N. Aceto, A. Bardia, D. T. Miyamoto, M. C. Donaldson, B. S. Wittner, J. A. Spencer, M. Yu, A. Pely, A. Engstrom, H. Zhu, B. W. Brannigan, R. Kapur, S. L. Stott, T. Shioda, S. Ramaswamy, D. T. Ting, C. P. Lin, M. Toner, D. A. Haber, S. Maheswaran Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis Cell 158 (2014), pp. 1110-1122.
[3] C. F. Laqbuschagne, E. C. Cheung, J. Blagih, M. C.. Domart, K. H. Vousden Cell clustering promotes a metabolic switch that supports metastatic colonization Cell Metab 30 (2019), pp. 720-734.
[4] I. J. Fidler The relationship of embolic homogeneity, number, size and visability to the incidence of experimental metastasis Eur J Canceer 9 (1973), pp. 223-227.
[5] I. J. Fidler The pathogenesis of cancer metastasis: the seed and soil hypothesis revisited Nat Rev Cancer 3 (2003), pp. 453-458.
[6] I. Zeidman, J. M. Buss Transpulmonary passage of tumor cell emboli Cancer Res 12 (1952), pp. 731-733.
[7] L. A. Liotta, M. G. Saidel, J. Kleinerman The significance of hematogenous tumor cell clumps in the metastatic process Cancer Res 36 (1976), pp. 889-894.
[8] V. Padmanaban, I. Krol, Y. Suhail, B. M. Szczerba, N. Aceto, J. S. Bader, A. J. Ewald E-cadherin is required for metastasis in multiple models of breast cancer Nature 573 (2019), pp. 439-444.
[9] M. E. Menyailo, M. S. Tretyakova, E. V. Denisov Heterogeneity of circulating tumor cells in breast cancer: identifying metastatic seeds Int. J. Mol. Sci 21 (2020), pp. 1696-1712.
[10] S. Gkountela, F. Castro-Giner, B. M. Szczerba, M. Vetter, J. Landin, R. Scherrer, I. Krol, M. C. Schneidmann, C. Beisel, C. U. Stirnimann, C. Kurzeder, Vheinzelnann-Schwarz, C. Rochlitz, W. P. Weber, N. Aceto Circulating tumor cell clustering shapes DNA methylation to enable metastasis seeding Cell 176 (2019) pp. 98-112.
[11] S. B. Oppenheimer Cellular basis of cancer metastasis Acta Histochem 108 (2006), pp. 327-334
[12] K. Germanovich, E. Allesandra Femiaq, C. Y. Cheng, N. Dovlatova, M. Cattaneo Effects of pH and concentration of sodium citrate anticoagulant on platelet aggregation measured by light transmission aggregometry induced by adenosine diphosphate Platelets 29 (2018) pp. 21-26.
[13] Kolodkin-Gal, S. Romero, S. Cao, J. Clardy, R. Kolter, R. Losick D-amino acids trigger biofilm disassembly Science 30 (2010), pp. 627-629.
[14] G Zem, O Tosunyan, A Hambarsoomian, K Lim, K Khatiblou, S Niamat E Choi, C Monroy, M Chavez, N Karaan, M Basmajian, S Kim, A Kurginyan, S Sorooshian, L Manzo, F Bahri,. A Holverson, G Chacon, N Allatabakhsh, C Irikyan, C Tortorice, S Balyan, N Amer, S Shtivelman, V Vahdati, T Kaur S Danialian, A Allard, L Jorshari, N Kazmi, N Sarkissian, K Mkhitarian, C Chavez, M Havaei, A Adzhemian, M Takakura, Y Huang, A Haritounian, A Arakelian, J Bohorquez, M Asatryan, Y Herrera, L Mayorga, A Garcia, S Oppenheimer Heirarchy of anti-clumping salts FASEB J 29 (2015), abstract id 52.
[15] V. Nahapetyan, S. Delos Santos, K. J. Crocker, D. Tobar, D. Nazarian, H. Chirishyan, G. Beltran, R. Dubin, L. Reque,, P. Singh, B. Cardona, G. Royce Bachinela, L. Sarkisyan, G. Zem, S. Oppenheimer A manual kinetic assay in a fixed yeast model for drug discovery American Journal of Applied Scientific Research 5 (2019) pp. 28-35.
[16] P. C. Zeidler-Erdely, J. M. Antonino, T. G. Meighan, S. H. Young, T. J. Eve, M. A. Hammer, A Erdely Comparison of cell counting methods in rodent pulmonary toxicity studies: automated and manual protocols and considerations for experimental design Inhal Toxicol 28 (2016), mpp. 410-420.
[17] S. B. Oppenheimer Lab training: undergraduate research in action Nature 519 (2015), p. 158.
[18] O. Herstein Steven Oppenheimer CSUN Magazine 67 (2016) p. 20.
[19] National Science Foundation, Presidential awards for excellence in science, mathematics and engineering mentoring NSF Home Page (2019). This is the highest U.S. national award for mentoring.
Cite This Article
  • APA Style

    Kristel Crocker, Jonie Deleon, Lucy Telliyan, Kevin Aprelian, Aryeh Rosenberg, et al. (2020). A Kinetic Assay for Drug Discovery: Part 2, Sodium Sulfate. American Journal of Applied Scientific Research, 6(2), 39-42. https://doi.org/10.11648/j.ajasr.20200602.12

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    ACS Style

    Kristel Crocker; Jonie Deleon; Lucy Telliyan; Kevin Aprelian; Aryeh Rosenberg, et al. A Kinetic Assay for Drug Discovery: Part 2, Sodium Sulfate. Am. J. Appl. Sci. Res. 2020, 6(2), 39-42. doi: 10.11648/j.ajasr.20200602.12

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    AMA Style

    Kristel Crocker, Jonie Deleon, Lucy Telliyan, Kevin Aprelian, Aryeh Rosenberg, et al. A Kinetic Assay for Drug Discovery: Part 2, Sodium Sulfate. Am J Appl Sci Res. 2020;6(2):39-42. doi: 10.11648/j.ajasr.20200602.12

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  • @article{10.11648/j.ajasr.20200602.12,
      author = {Kristel Crocker and Jonie Deleon and Lucy Telliyan and Kevin Aprelian and Aryeh Rosenberg and Nikole Pouri and Gerard Beltran and Vivian Ramirez and David Kaufman and Arpineh Petrosyan and Deanna Nazarian and Monikajane Magistrado and Suren Matinian and Daniel Hanna and Sera Eskandari and Faisal Atanante and Adees Nerses and Greg Zem and Steven Oppenheimer},
      title = {A Kinetic Assay for Drug Discovery: Part 2, Sodium Sulfate},
      journal = {American Journal of Applied Scientific Research},
      volume = {6},
      number = {2},
      pages = {39-42},
      doi = {10.11648/j.ajasr.20200602.12},
      url = {https://doi.org/10.11648/j.ajasr.20200602.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajasr.20200602.12},
      abstract = {Clumped cells are generally more dangerous than single cells in cancer spread, thrombocytosis and biofilm infectivity. Here a simple direct kinetic assay is used to examine a specific reagent for anti-clumping activity using a Prefer fixed yeast (Saccharomyces cerevisiae) model that has been recently described by us in detail using other reagents. In 1212 trials by 17 investigators sodium sulfate (1-3 mg per ml deionized water) was examined by measuring percentage single cells, number of clumps and number of cells per clump over a 60 min time course, with standard deviations and t-tests to determine any significant differences between controls and experimentals. Sodium sulfate showed sometimes inconsistent unclumping activity especially in magnitude of effects. When percentage of single cells increased, clump number and/or number of cells per clump generally decreased, helping to validate the assay. An example of these findings in 60 trials at 60 min with 1-3 mg sodium sulfate per ml deionized water: 1 mg 15% increased singles (p0.05); 2 mg 12% increased singles (p<0.01), 20% decreased clumps (p<0.01), 30% decreased cells per clump (p<0.01); 3 mg 27% increased singles (p<0.01), 36% decreased clumps (p<0.01), 28% decreased cells per clump (p<0.02). Here sodium sulfate showed promise as an anti-cell-clumping reagent together with sodium citrate reported previously in part 1 of this study. Sodium citrate is a known human anticoagulant independently identified with this assay, helping to validate the assay for drug discovery applications.},
     year = {2020}
    }
    

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    T1  - A Kinetic Assay for Drug Discovery: Part 2, Sodium Sulfate
    AU  - Kristel Crocker
    AU  - Jonie Deleon
    AU  - Lucy Telliyan
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    AU  - Aryeh Rosenberg
    AU  - Nikole Pouri
    AU  - Gerard Beltran
    AU  - Vivian Ramirez
    AU  - David Kaufman
    AU  - Arpineh Petrosyan
    AU  - Deanna Nazarian
    AU  - Monikajane Magistrado
    AU  - Suren Matinian
    AU  - Daniel Hanna
    AU  - Sera Eskandari
    AU  - Faisal Atanante
    AU  - Adees Nerses
    AU  - Greg Zem
    AU  - Steven Oppenheimer
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    PY  - 2020
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    DO  - 10.11648/j.ajasr.20200602.12
    T2  - American Journal of Applied Scientific Research
    JF  - American Journal of Applied Scientific Research
    JO  - American Journal of Applied Scientific Research
    SP  - 39
    EP  - 42
    PB  - Science Publishing Group
    SN  - 2471-9730
    UR  - https://doi.org/10.11648/j.ajasr.20200602.12
    AB  - Clumped cells are generally more dangerous than single cells in cancer spread, thrombocytosis and biofilm infectivity. Here a simple direct kinetic assay is used to examine a specific reagent for anti-clumping activity using a Prefer fixed yeast (Saccharomyces cerevisiae) model that has been recently described by us in detail using other reagents. In 1212 trials by 17 investigators sodium sulfate (1-3 mg per ml deionized water) was examined by measuring percentage single cells, number of clumps and number of cells per clump over a 60 min time course, with standard deviations and t-tests to determine any significant differences between controls and experimentals. Sodium sulfate showed sometimes inconsistent unclumping activity especially in magnitude of effects. When percentage of single cells increased, clump number and/or number of cells per clump generally decreased, helping to validate the assay. An example of these findings in 60 trials at 60 min with 1-3 mg sodium sulfate per ml deionized water: 1 mg 15% increased singles (p0.05); 2 mg 12% increased singles (p<0.01), 20% decreased clumps (p<0.01), 30% decreased cells per clump (p<0.01); 3 mg 27% increased singles (p<0.01), 36% decreased clumps (p<0.01), 28% decreased cells per clump (p<0.02). Here sodium sulfate showed promise as an anti-cell-clumping reagent together with sodium citrate reported previously in part 1 of this study. Sodium citrate is a known human anticoagulant independently identified with this assay, helping to validate the assay for drug discovery applications.
    VL  - 6
    IS  - 2
    ER  - 

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Author Information
  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

  • Department of Biology and Center for Cancer and Developmental Biology, California State University Northridge, Northridge, California, United States

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