The Journal of Korean Obstetrics and Gynecology (대한한방부인과학회지)

The Society of Korean Medicine Obstetrics and Gynecology (대한한방부인과학회)
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Research on the Anti-Breast Cancer and Anti-Inflammatory Effects of Chungganhaewool-tang and Shipyeukmiyeugi-eum

청간해울탕(淸肝解鬱湯)과 십륙미유기음(十六味流氣飮)의 유방암에 대한 항암, 항염 효능 연구

  • Ryu, Hyo-Kyung (Wolya Korean Medical Clinic) ;
  • Jung, Min-Jae (Dept. of Korean Medicine Rehabilitation, College of Korean Medicine, Dong-shin University) ;
  • Cho, Seong-Hee (Dept. of Korean Gynecology and Obstetrics, College of Korean Medicine, Dong-Shin University)
  • 류효경 (월야한의원) ;
  • 정민재 (동신대학교 한의과대학 한방재활의학과교실) ;
  • 조성희 (동신대학교 한의과대학 한방부인과교실)
  • Received : 2022.04.08
  • Accepted : 2022.08.26
  • Published : 2022.08.26
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Abstract

Objectives: The purpose of this study is to evaluate anti-breast cancer and anti-inflammatory effects of Chungganhaewool-tang and Shipyeukmiyeugi-eum. Methods: MDA-MB-231 cells were used to measure cytotoxicity, Reactive oxygen species (ROS) production, protein expression amounts of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), Cytochrome C Caspase-3, Caspase-7, Caspase-9, Poly ADP-ribose polymerase (PARP), Nuclear factor erythroid-2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1) and NAD (P) H Quinone Oxidoreductase 1 (NQO1) to evaluate the anti-breast cancer effects of Chungganhaewool-tang (CHT) and Shipyeukmiyeugi-eum (SYE), and THP-1 cells, differentiated into macrophage and induced inflammation with Lipopolysaccharide (LPS), were used to measure production amounts of ROS, Nitric oxide (NO), and protein expression amounts of Inducible nitric oxide synthase (iNOS), Cyclooxygenase (COX-2), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-α) to evaluate the anti-inflammatory effects of CHT and SYE. Results: CHT and SYE reduced MDA-MB-231 cell counts, increased protein expression of Bax and Cytochrome C, and decreased protein expression of Bcl-2, Bcl-xl. The protein expression amounts of Caspase-3, 7, and 9 decreased, but amounts of the active form, cleaved Caspase-3, 7, and 9, increased. In addition, PARP protein expression decreased, the amount of PARP protein in the cleaved form increased, and the amount of protein expressions of Nrf2 and HO-1 decreased, but NQO1 showed no significant difference. In THP-1 cells CHT and SYE reduced ROS and NO, and reduced protein expressions of iNOS, COX-2, IL-1, and TNF-α, but only SYE groups reduced IL-6. Conclusions: This study suggests that CHT and SYE have potential to be used as treatments for breast cancer.

Keywords

References

  1. Sung HA, et al.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.CA: CA Cancer J Clin.2021;71(3):209-49. https://doi.org/10.3322/caac.21660
  2. Korea Central Cancer Registry. National Cancer Center. Annual report of cancer statistics in Korea in 2018. Ministry of Health and Welfare. 2020:22.
  3. Park JG, Bang YJ, Ha SW. Oncology. Rev. ed. Seoul:Ilchokak. 2012:596-7, 606-44.
  4. Jo HI.A general perspective on breast disease and training system for breast cancer specialists in Europe.Obstet Gynecol Sci.2010;53(7):565-78.
  5. Noh OK, et al.Probabilities of Pulmonary and Cardiac Complications and Radiographic Parameters in Breast Cancer Radiotherapy. Radiat Oncol J.2010;28(1):23-31
  6. Smoot B, Wampler M, Topp KS.Breast Cancer Treatments and Complications: Implications for Rehabilitation.Phys Ther J Policy Adm Leadersh.2009;27(3) :16-26.
  7. Kayl AE, Meyers CA.Side-effects of chemotherapy and quality of life in ovarian and breast cancer patients. Curr Opin Gynecol Obstet.2006;18(1) :24-8. https://doi.org/10.1097/01.gco.0000192996.20040.24
  8. Dodd MJ, Miaskowski C, Paul SM. Symptom clusters and their effect on the functional status of patients with cancer.Oncol Nurs Forum.2001;28(3) :465-70.
  9. Lee TB, Jub JH.Can Hinokitiol Kill Cancer Cells? Alternative Therapeutic Anticancer Agent via Autophagy and Apoptosis.Korean J Clin Lab Sci. 2019;51(2):221-34. https://doi.org/10.15324/kjcls.2019.51.2.221
  10. Oh HN, et al.Anticancer Effect of Paedoksans for Oral Squamous Cell Carcinoma and Malignant Pleural Mesothelioma.Saengyak Hakhoe Chi. 2017;48(3):213-8.
  11. Cho SS, et al.Anticancer Activity and Chemical Composition of a Non-Polar Fraction from Asiasari Radix et Rhizoma.Saengyak Hakhoe Chi.2020;51(4):264-9.
  12. Nam KY, et al.Recent Progress in Research on Anticancer Activities of Ginsenoside-Rg3.Saengyak Hakhoe Chi.2014;45(1):1-10.
  13. Song JY, et al.Screening of Antineoplastic Immunomodulator from Herbal Medicines. Yakhak Hoeji.1998;42(2):132-9.
  14. Han DS, et al.Development of Anticancer Agents from Korean Medicinal Plants (Part 10).The Growth-inhibitory Effect of Taraxaci Herba Extract Against Human Skin Melamoma Cells. J.Toxicol.Pub.Health.1998;14(4) :489-94.
  15. The Society of Korean Medicine Obstetrics & Gynecology. Korean Medicine Obstetrics and Gynecology (Vol 2). 4th rev. ed. Seoul:Euiseongdang. 2021:459, 466-7.
  16. Shin JY. (申載鏞). Bangyakhappyeonhaeseol (方藥合編解說). Seoul:Shingwang-munhwasa. 1993:178-9.
  17. Seo BI, Kim MJ.A clinical study on a patient with postpartum depression and acute mastitis.Kor.J.Herbology. 2003;18(1):145-8.
  18. Yi JE, Kim BW.Effects of Sipyukmiyukieum on DNA Synthesis, cAMP Synthesis and MHC-class II Expression of FRTL-5 Thyroid Cells.Korean J. Orient.Int.Med.2005;26(2):398-408.
  19. Jeoung YH, Chae BY.Studies on Effects of Sipyukmiyuki-eum on the Hyperthyroidism.The Journal of K.O.M.S.1988;9(2):98-108.
  20. Jung YC, Park YS, Kim DC.Shipyeukmiyeugieum Extracts Suppressed Tumor Growth through Immunomodulatory Effects on MCF-7.The Journal of Oriental Obstetrics & Gynecology.2012; 25(3):40-60.
  21. Allavena P, et al.Pathways connecting inflammation and cancer.Curr Opin Genet Dev.2008;18(1):3-10. https://doi.org/10.1016/j.gde.2008.01.003
  22. Heo J(許浚). Donguibogam(東醫寶鑑). Seoul:Bubin-munhwasa. 2012:764-6.
  23. Lowe SW, Lin AW.Apoptosis in Cancer. Carcinogenesis.2000;21(3):485-95. https://doi.org/10.1093/carcin/21.3.485
  24. Hanahan D, Weinberg RA.Hallmarks of Cancer: the Next Generation.Cell. 2011;144(5):646-74. https://doi.org/10.1016/j.cell.2011.02.013
  25. Greten FR, Grivennikov SI.Inflammation and Cancer: Triggers, Mechanisms, and Consequences.Immunity.2019;51(1) :27-41. https://doi.org/10.1016/j.immuni.2019.06.025
  26. Kapuscinski J.DAPI: a DNA-Specific Fluorescent Probe.Biotech Histochem. 1995;70(5):220-33. https://doi.org/10.3109/10520299509108199
  27. Doonan F, Cotter TG.Morphological assessment of apoptosis.Methods. 2008;44(3):200-4. https://doi.org/10.1016/j.ymeth.2007.11.006
  28. Perillo B, et al.ROS in cancer therapy: the bright side of the moon.Exp Mol Med.2020;52(2):192-203. https://doi.org/10.1038/s12276-020-0384-2
  29. Loboda A, et al.Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism.Cell Mol Life Sci.2016;73(17):3221-47. https://doi.org/10.1007/s00018-016-2223-0
  30. Wong PK, et al.Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2.Carcinogenesis. 2008;29(6):1235-43. https://doi.org/10.1093/carcin/bgn095
  31. Hassan M, et al.Apoptosis and molecular targeting therapy in cancer.Biomed Res Int.2014;2014:1-23.
  32. Budd RC.Death receptors couple to both cell proliferation and apoptosis. J Clin Invest.2002;109(4):437-78. https://doi.org/10.1172/JCI15077
  33. Renault TT, Dejean LM, Manon S.A brewing understanding of the regulation of Bax function by Bcl-xL and Bcl-2. Mech Ageing Dev.2017;161:201-10. https://doi.org/10.1016/j.mad.2016.04.007
  34. Zimmermann KC, Bonzon C, Green DR.The machinery of programmed cell death.Pharmacol Ther.2001; 92(1):57-70.
  35. Boulares AH, et al.Role of Poly (ADP-ribose) Polymerase (PARP) Cleavage in Apoptosis.J Biol Chem. 1999;274(33):22932-40. https://doi.org/10.1074/jbc.274.33.22932
  36. Multhoff G, Molls M, Radons J.Chronic inflammation in cancer development. Front Immunol.2011;2:1-17. https://doi.org/10.3389/fimmu.2011.00001
  37. Wiseman H, Halliwell B.Damage to DNA by Reactive Oxygen and Nitrogen Species: Role in Inflammatory Disease and Progression to Cancer.Biochem. J.1996;313:17-29. https://doi.org/10.1042/bj3130017
  38. Shrihari TG.Inflammation Related Cancer - Highlights.J Carcinog Mutagen. 2016;7(3):2157-8.
  39. Chiarugi V, Magnelli L, Gallo O.Cox-2, iNOS and p53 as play-makers of tumor angiogenesis.Int J Mol Med. 1998;2(6):715-24.
  40. Sethi G, Sung BK, Aggarwal BB.TNF: a master switch for inflammation to cancer.Front Biosci.2008;13(13):5094-201. https://doi.org/10.2741/3066
  41. Guo YQ, et al.Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev.2012;38(7):904-10. https://doi.org/10.1016/j.ctrv.2012.04.007
  42. Laird BJ, et al.The Emerging Role of Interleukin 1β (IL-1β) in Cancer Cachexia.Inflammation.2021;44(4) :1223-8. https://doi.org/10.1007/s10753-021-01429-8
  43. Vaux DL, Gerl R.Apoptosis in the development and treatment of cancer. Carcinogenesis.2005;26(2):263-333. https://doi.org/10.1093/carcin/bgh283