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BRCA1-DEFICIENT CANCER CELLS TAKE
      ADVANTAGE OF DNA.


SILIBININ KILLS SKIN CELLS MUTATED BY
            UVA RADIATION.
          REPAIR MECHANISM.

                        Tatiana Gil Franco
                         Medicine Student
                              3° semestre
                                    U.P.B
Introduction


   The BRCA1 protein helps
    to mend double-strand
    DNA breaks by promoting
    homologous
    recombination.

   Silibinin, kills skin cells
    mutated by UVA radiation
    and protects against
    damage by UVB
    radiation.
BRCA1-deficient
 cancer cells take
advantage of DNA
      repair
   mechanism.
  The Journal of Cell
       Biology.
     (Jan 22, 2013)
BRCA1-DEFICIENT CANCER CELLS TAKE
ADVANTAGE OF DNA REPAIR MECHANISM

BRCA1

   It’s a human caretaker gene
    that produces a protein
    called breast cancer type 1
    susceptibility protein,
    responsible for repairing
    DNA.

   The BRCA1 protein helps to
    mend double-strand DNA
    breaks by promoting
    homologous recombination.
BRCA1-DEFICIENT CANCER CELLS TAKE
ADVANTAGE OF DNA REPAIR MECHANISM

53BPA1                          Cathepsin L

   It’s a protein that helps      It’s a protease that
    orchestrate a different         destroys 53BP1 by
    DNA repair                      entering the nucleus.
    mechanism,
    nonhomologous end              vitamin D is a
    joining (NHEJ)                  cathepsin L inhibitor

   Cells lacking BRCA1
    compensate by cutting
    back on 53BP1.
BRCA1-DEFICIENT CANCER CELLS TAKE
ADVANTAGE OF DNA REPAIR MECHANISM


   When they cultured breast cancer cells that were missing
    BRCA1, the cells stopped growing. After two weeks of
    lethargy, however, BOGA cells (BRCA1-deficient cells that
    overcome growth arrest), began to divide again.

   These cells showed increased levels of cathepsin L and
    reduced amounts of 53BP1.

   Eliminating cathepsin L from BOGA cells or dosing them with
    vitamin D, a cathepsin L inhibitor, prevented the decline in
    53BP1 abundance.
PERSONAL OPINION



           This article explains how cancer
              cells by cathepsin, 53BP1
             attack, inhibiting DNA repair
            mechanism. I think this is very
          important because the authors are
           proposing a treatment for breast
                        cancer.
Silibinin kills skin
 cells mutated by
UVA radiation and
 protects against
      cancer.
 Photochemistry and
   photobiology.
    (Jan. 31, 2013 )
SILIBININ KILLS SKIN CELLS MUTATED BY UVA
RADIATION AND PROTECTS AGAINST CÁNCER

    Silibinin, also known
     as silybin, is the major
     active         constituent
     of       silymarin,      a
     standardized extract of
     the milk thistle seeds
     containing         mixture
     of flavonolignans.              Silibinin    has    also
                                      demonstrated in vitro
                                      anti-cancer      effects,
                                      estrogen      dependent
                                      and         independent
                                      human             breast
                                      carcinoma cells.
SILIBININ KILLS SKIN CELLS MUTATED BY UVA
RADIATION AND PROTECTS AGAINST CÁNCER

   The first study, published
    in                      the
    journal    Photochemistry
    and Photobiology worked
    with human skin cells
    subjected      to     UVA
    radiation.

   The Agarwal Lab treated
    these UVA-affected cells
    with       silibinin.   With
    silibinin, the rate at which
    these damaged cells died
    increased dramatically.
SILIBININ KILLS SKIN CELLS MUTATED BY UVA
RADIATION AND PROTECTS AGAINST CÁNCER

                           The second study shows
                            that       instead     of
                            beneficially killing cells
                            damaged        by    UVA
                            radiation, treatment with
                            silibinin protects human
                            skill cells from damage
                            by UVB radiation.

                           The UVB radiation makes
                            up about 5 percent of the
                            sun's radiation reaching
                            Earth.
PERSONAL OPINION



          I think that it’s a very important new
          because this tell us about the great
            damage that UV light causes us
           and show us how with the help of
              the silibinin and a DNA repair
               mechanism can prevent this
                          damage.
MEDICAL UTILITY
   Knowing about the mechanisms of DNA repair is
    very important in the field of medicine as these
    mechanisms are closely linked to health problems
    such as cancer.
MEDICAL UTILITY




                    In the first news tell us
                   about breast cancer and
                      the BRCA1 protein
                  function in this pathology.
MEDICAL UTILITY




                  The second new describe
                     us the operation of
                     silibinin killing cells
                   damaged by UV rays.
REFERENCES
   News medical “Silibinin kills skin cells mutated by UVA radiation and protects
    against cáncer”
Jan 31, 2013. Photochemistry and photobiology.
< http://www.news-medical.net/news/20130131/Silibinin-kills-skin-cells-mutated-by-
UVA-radiation-and-protects-against-cancer.aspx>


   News medical “BRCA1-deficient cancer cells take advantage of DNA repair
    mechanism”
Jan 22, 2013. The Journal of Cell Biology.
<http://www.news-medical.net/news/20130122/BRCA1-deficient-cancer-cells-take-
advantage-of-DNA-repair-mechanism.aspx>


   MARTINEZ SÁNCHEZ, Lina María. Biología molecular. 2. ed. Medellín: UPB.
    Fac. de Medicina, 2006. 208 p.
DNA Repair Mechanisms

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DNA Repair Mechanisms

  • 1. BRCA1-DEFICIENT CANCER CELLS TAKE ADVANTAGE OF DNA. SILIBININ KILLS SKIN CELLS MUTATED BY UVA RADIATION. REPAIR MECHANISM. Tatiana Gil Franco Medicine Student 3° semestre U.P.B
  • 2.
  • 3.
  • 4. Introduction  The BRCA1 protein helps to mend double-strand DNA breaks by promoting homologous recombination.  Silibinin, kills skin cells mutated by UVA radiation and protects against damage by UVB radiation.
  • 5. BRCA1-deficient cancer cells take advantage of DNA repair mechanism. The Journal of Cell Biology. (Jan 22, 2013)
  • 6. BRCA1-DEFICIENT CANCER CELLS TAKE ADVANTAGE OF DNA REPAIR MECHANISM BRCA1  It’s a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA.  The BRCA1 protein helps to mend double-strand DNA breaks by promoting homologous recombination.
  • 7. BRCA1-DEFICIENT CANCER CELLS TAKE ADVANTAGE OF DNA REPAIR MECHANISM 53BPA1 Cathepsin L  It’s a protein that helps  It’s a protease that orchestrate a different destroys 53BP1 by DNA repair entering the nucleus. mechanism, nonhomologous end  vitamin D is a joining (NHEJ) cathepsin L inhibitor  Cells lacking BRCA1 compensate by cutting back on 53BP1.
  • 8. BRCA1-DEFICIENT CANCER CELLS TAKE ADVANTAGE OF DNA REPAIR MECHANISM  When they cultured breast cancer cells that were missing BRCA1, the cells stopped growing. After two weeks of lethargy, however, BOGA cells (BRCA1-deficient cells that overcome growth arrest), began to divide again.  These cells showed increased levels of cathepsin L and reduced amounts of 53BP1.  Eliminating cathepsin L from BOGA cells or dosing them with vitamin D, a cathepsin L inhibitor, prevented the decline in 53BP1 abundance.
  • 9. PERSONAL OPINION This article explains how cancer cells by cathepsin, 53BP1 attack, inhibiting DNA repair mechanism. I think this is very important because the authors are proposing a treatment for breast cancer.
  • 10. Silibinin kills skin cells mutated by UVA radiation and protects against cancer. Photochemistry and photobiology. (Jan. 31, 2013 )
  • 11. SILIBININ KILLS SKIN CELLS MUTATED BY UVA RADIATION AND PROTECTS AGAINST CÁNCER  Silibinin, also known as silybin, is the major active constituent of silymarin, a standardized extract of the milk thistle seeds containing mixture of flavonolignans.  Silibinin has also demonstrated in vitro anti-cancer effects, estrogen dependent and independent human breast carcinoma cells.
  • 12. SILIBININ KILLS SKIN CELLS MUTATED BY UVA RADIATION AND PROTECTS AGAINST CÁNCER  The first study, published in the journal Photochemistry and Photobiology worked with human skin cells subjected to UVA radiation.  The Agarwal Lab treated these UVA-affected cells with silibinin. With silibinin, the rate at which these damaged cells died increased dramatically.
  • 13. SILIBININ KILLS SKIN CELLS MUTATED BY UVA RADIATION AND PROTECTS AGAINST CÁNCER  The second study shows that instead of beneficially killing cells damaged by UVA radiation, treatment with silibinin protects human skill cells from damage by UVB radiation.  The UVB radiation makes up about 5 percent of the sun's radiation reaching Earth.
  • 14. PERSONAL OPINION I think that it’s a very important new because this tell us about the great damage that UV light causes us and show us how with the help of the silibinin and a DNA repair mechanism can prevent this damage.
  • 15.
  • 16. MEDICAL UTILITY  Knowing about the mechanisms of DNA repair is very important in the field of medicine as these mechanisms are closely linked to health problems such as cancer.
  • 17. MEDICAL UTILITY In the first news tell us about breast cancer and the BRCA1 protein function in this pathology.
  • 18. MEDICAL UTILITY The second new describe us the operation of silibinin killing cells damaged by UV rays.
  • 19. REFERENCES  News medical “Silibinin kills skin cells mutated by UVA radiation and protects against cáncer” Jan 31, 2013. Photochemistry and photobiology. < http://www.news-medical.net/news/20130131/Silibinin-kills-skin-cells-mutated-by- UVA-radiation-and-protects-against-cancer.aspx>  News medical “BRCA1-deficient cancer cells take advantage of DNA repair mechanism” Jan 22, 2013. The Journal of Cell Biology. <http://www.news-medical.net/news/20130122/BRCA1-deficient-cancer-cells-take- advantage-of-DNA-repair-mechanism.aspx>  MARTINEZ SÁNCHEZ, Lina María. Biología molecular. 2. ed. Medellín: UPB. Fac. de Medicina, 2006. 208 p.