Acta Scientific Cancer Biology (ASCB)

Review Article Volume 4 Issue 6

Sulforaphane: Mechanisms of Epigenetic Reversion and its Anti-Carcinogenic Pathways as Potential Adjunctive Treatment in Cancer

Andre da Silva Santos1,2, Sandra Maria Matta3,4* and Henry Okigami5

1Medical Director, Clinical Oncologist at the Center for Integrative Oncology and Prevention (COIP), São Paulo, Brazil
2Scientific Director of G8 Integrative, São Paulo, Brazil
3Nutrigeneticist and Registered Dietitian, Clinical Oncologist at the Center for Integrative Oncology and Prevention (COIP), São Paulo, Brazil
4Scientific Director in Nutrition/Nutritional Genomics/Oncogenetic of G8 Integrative, São Paulo, Brazil
5Director of Science and Technology, Pharmaceutical Biochemist at the Center for Integrative Oncology and Prevention (COIP), São Paulo, Brazil

*Corresponding Author: Sandra Maria Matta, Nutrigeneticist and Registered Dietitian, Clinical Oncologist at the Center for Integrative Oncology and Prevention (COIP), São Paulo, Brazil.

Received: February 29, 2020; Published: May 29, 2020

×

Abstract

 Estimates of cancer in Brazil and the salty world each year, placing it at the top of the death causes ranking.
The first and last year of 2007 was 7.6 million in 2007, showing a 32% increase in deaths between 2000 and 2007. In 2007, the cancer was responsible for 13% of all deaths in the world [1,2].
Like what is in Brazil, what is a more common cause of death, the elimination of accidents and cerebrovascular disease. In 2014, 395,000 new cases of cancer were found, 205,000 in men and 190,000 in women. The most incident types of cancer are prostate, lung, colon and rectum. In women, the most common cancers are breast, colon and rectum, cervix, lung and thyroid, according to INCA data. Estimate 2014: Incidence of Cancer in Brazil. 2014; Rio de Janeiro: INCA, 124p.
This is a challenge to prevent the preventive decision of the prevention of the risk of the treatment of treatment and treatment of debilitating disease.
Thus, sulforaphane (SFN) is a natural isothiocyanate derived from cruciferous vegetables, such as broccoli, cabbage, watercress, arugula, kale, etc.
This phytoactive product (isothiocyanate) acts in cellular destiny through the nutritionist dietitian, although after an observation that dietetics are not detected in the urine is an indication that they are not absorbed [3]. In addition, there are sessions available so that the apparatus cannot convert glycosinolates to isothiocyanates [4]. However, they include literacy shows that glycosinolates dietetic they best converted in isothiocyanates in animals and humans, and that this migration is mediated by the activity of myrosinase of the enteric microflora [3,5,6]. Once generated, isothiocyanates are absorbed and metabolized by sequential enzyme waves, a first of which is a conjugation with glutathione [7,8].

Keywords: Sulforaphane (SFN); Isothiocyanate; Cancer

×

References

  1. Yılmaz HH., et al. “Cancer trends and incidence and mortality patterns in Turkey”. Japanese Journal of Clinical Oncology 1 (2011): 10-16.
  2. Bray F., et al. “Global estimates of cancer prevalence for 27 sites in the adult population in 2008”. International Journal of Cancer 5 (2013): 1133-1145.
  3. Shapiro TA., et al. “Human metabolism and excretion of cancer chemoprotective glucosinolates and isothiocyanates of cruciferous vegetables”. Cancer Epidemiology, Biomarkers and Prevention 7.12 (1998): 1091-100.
  4. Fahey JW., et al. “The chemical diversity and distribution of glucosinolates and isothiocyanates among plants”. Phytochemistry1 (2001): 5-51.
  5. Rabot S., et al. “Rape-seed meal toxicity in gnotobiotic rats: influence of a whole human faecal flora or single human strains of Escherichia coli and Bacteroides vulgatus”. British Journal of Nutrition 1 (1993): 323-331.
  6. Getahun SM and Chung FL. “Conversion of glucosinolates to isothiocyanates in humans after ingestion of cooked watercress”. Cancer Epidemiology, Biomarkers and Prevention 5 (1999): 447-451.
  7. Zhang Y., et al. “Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases”. Biochemical and Biophysical Research Communications 2 (1995): 748-755.
  8. Kolm RH., et al. “Isothiocyanates as substrates for human glutathione transferases: structure-activity studies”. Biochemical Journal 2 (1995): 453-459.
  9. Cheng Y-M., et al. “Sulforaphane, a Dietary Isothiocyanate, Induces G₂/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45β/CDC2 Association”. International Journal of Molecular Sciences 9 (2016): 1530.
  10. Peng X., et al. “Sulforaphane inhibits invasion by phosphorylating ERK1/2 to regulate E-cadherin and CD44v6 in human prostate cancer DU145 cells”. Oncology Reports 3 (2015): 1565-1572.
  11. Leone A., et al. “Sulforaphane for the chemoprevention of bladder cancer: molecular mechanism targeted approach”. Oncotarget21 (2017): 35412-35424.
  12. Juengel E., et al. “Sulforaphane inhibits proliferation and invasive activity of everolimus-resistant kidney cancer cells In vitro”. Oncotarget 51 (2016): 85208-85219.
  13. Wang D-X., et al. “Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3β/β-catenin signaling pathways”. Acta Pharmaceutica Sinica 2 (2017): 241-251.
  14. Clarke JD., et al. “Multi-targeted prevention of cancer by sulforaphane”. Cancer Letters 2 (2008): 291-304.
  15. Wang X., et al. “Sulforaphane improves chemotherapy efficacy by targeting cancer stem cell-like properties via the miR-124/IL-6R/STAT3 axis”. Scientific Reports 6 (2016): 36796.
  16. Żuryń A., et al. “The effect of sulforaphane on the cell cycle, apoptosis and expression of cyclin D1 and p21 in the A549 non-small cell lung cancer cell line”. International Journal of Oncology 6 (2016): 2521-2533.
  17. Kim S-H., et al. “Sulforaphane sensitizes human breast cancer cells to paclitaxel-induced apoptosis by downregulating the NF-κB signaling pathway”. Oncology Letters 6 (2017): 4427-4432.
  18. Talalay P. “Chemoprotection against cancer by induction of phase 2 enzymes”. Bio Factors 1-4 (2000): 5-11.
  19. Talalay P. “Mechanisms of induction of enzymes that protect against chemical carcinogenesis”. Advances in Enzyme Regulation 28 (1989): 237-250.
  20. Zhao J., et al. “Hypoxia-Targeting Organometallic Ru(II)-Arene Complexes with Enhanced Anticancer Activity in Hypoxic Cancer Cells”. Inorganic Chemistry 14 (2018): 8396-8403.
  21. Pastorek M., et al. “Sulforaphane reduces molecular response to hypoxia in ovarian tumor cells independently of their resistance to chemotherapy”. International Journal of Oncology 1 (2015): 51-60.
  22. Kim DH., et al. “Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells”. International Journal of Oncology 6 (2015): 2226-2232.
  23. Cadenas E. “Biochemistry of oxygen toxicity”. Annual Review of Biochemistry 58 (1989): 79-110.
  24. Meeran SM., et al. “Epigenetic targets of bioactive dietary components for cancer prevention and therapy”. Clinical Epigenetics 3-4 (2010): 101-116.
  25. Gerhauser C. “Epigenetic impact of dietary isothiocyanates in cancer chemoprevention”. Current Opinion in Clinical Nutrition and Metabolic Care 4 (2013): 405-410.
  26. Kensler TW., et al. “Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane”. Topics in Current Chemistry 329 (2013): 163-177.
  27. Narendhirakannan RT and Hannah MAC. “Oxidative stress and skin cancer: an overview”. Indian Journal of Clinical Biochemistry 2 (2013): 110-115.
  28. Johnson GS., et al. “A functional pseudogene, NMRAL2P, is regulated by Nrf2 and serves as a coactivator of NQO1 in sulforaphane-treated colon cancer cells”. Molecular Nutrition and Food Research 4 (2017).
  29. Liu M., et al. “Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels”. Bio Factors1 (2015): 52-57.
  30. Dinkova-Kostova AT., et al. “Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants”. Proceedings of the National Academy of Sciences of the United States of America 18 (2002): 11908-11913.
  31. Basten GP., et al. “Sulforaphane and its glutathione conjugate but not sulforaphane nitrile induce UDP-glucuronosyl transferase (UGT1A1) and glutathione transferase (GSTA1) in cultured cells”. Carcinogenesis8 (2002): 1399-1404.
  32. Thimmulappa RK., et al. “Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray”. Cancer Research 18 (2002): 5196-5203.
  33. Hu R., et al. “Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice”. Cancer Letters 2 (2006): 170-192.
  34. Hu C., et al. “Modification of keap1 cysteine residues by sulforaphane”. Chemical Research in Toxicology 4 (2011): 515-521.
  35. Mondal A., et al. “Sulforaphene promotes Bax/Bcl2, MAPK-dependent human gastric cancer AGS cells apoptosis and inhibits migration via EGFR, p-ERK1/2 down-regulation”. General Physiology and Biophysics 1 (2016): 25-34.
  36. Magesh S., et al. “Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents”. Medicinal Research Reviews 4 (2012): 687-726.
  37. Qin S and Hou D-X. “Multiple regulations of Keap1/Nrf2 system by dietary phytochemicals”. Molecular Nutrition and Food Research 8 (2016): 1731-1755.
  38. Zhang C., et al. “Sulforaphane enhances Nrf2 expression in prostate cancer TRAMP C1 cells through epigenetic regulation”. Biochemical Pharmacology 9 (2013): 1398-1404.
  39. Su Z-Y., et al. “Requirement and epigenetics reprogramming of Nrf2 in suppression of tumor promoter TPA-induced mouse skin cell transformation by sulforaphane”. Cancer Prevention Research 3 (2014): 319-329.
  40. Shapiro TA., et al. “Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study”. Nutrition and Cancer 1 (2006): 53-62.
  41. Cornblatt BS., et al. “Preclinical and clinical evaluation of sulforaphane for chemoprevention in the breast”. Carcinogenesis7 (2007): 1485-1490.
  42. Alumkal JJ., et al. “A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer”. Investigational New Drugs 2 (2015): 480-489.
  43. Lozanovski VJ., et al. “Pilot study evaluating broccoli sprouts in advanced pancreatic cancer (POUDER trial) - study protocol for a randomized controlled trial”. Trials 15 (2014): 204.
  44. Clarke JD., et al. “Comparison of isothiocyanate metabolite levels and histone deacetylase activity in human subjects consuming broccoli sprouts or broccoli supplement”. Journal of Agricultural and Food Chemistry 20 (2011): 10955-10963.
  45. Myzak MC., et al. “Sulforaphane retards the growth of human PC-3 xenografts and inhibits HDAC activity in human subjects”. Experimental Biology and Medicine 2 (2007): 227-234.
×

Citation

Citation: Sandra Maria Matta., et al. “Sulforaphane: Mechanisms of Epigenetic Reversion and its Anti-Carcinogenic Pathways as Potential Adjunctive Treatment in Cancer”.Acta Scientific Cancer Biology 4.6 (2020): 21-25.




Metrics

Acceptance rate35%
Acceptance to publication20-30 days
Impact Factor1.018

Indexed In




News and Events


  • Certification for Review
    Acta Scientific certifies the Editors/reviewers for their review done towards the assigned articles of the respective journals.
  • Submission Timeline for Upcoming Issue
    The last date for submission of articles for regular Issues is December 15, 2021.
  • Publication Certificate
    Authors will be issued a "Publication Certificate" as a mark of appreciation for publishing their work.
  • Best Article of the Issue
    The Editors will elect one Best Article after each issue release. The authors of this article will be provided with a certificate of “Best Article of the Issue”.
  • Welcoming Article Submission
    Acta Scientific delightfully welcomes active researchers for submission of articles towards the upcoming issue of respective journals.
  • Contact US