Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
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Induction of Apoptosis by Gamma-Irradiated Apigenin in H1975 Human Non-Small Lung Cells

감마선 조사된 Apigenin의 H1975 인체 비소폐암세포에서의 Apoptosis 유발 효과

  • Park, Jae-Nam (Advance Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Byun, Eui-Baek (Advance Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Kim, Jwa-Jin (Department of Anatomy, College of Medicine, Konyang University) ;
  • Jang, Beon-Su (Advance Radiation Technology Institute, Korea Atomic Energy Research Institute) ;
  • Park, Sang-Hyun (Advance Radiation Technology Institute, Korea Atomic Energy Research Institute)
  • 박재남 (한국원자력연구원 첨단방사선연구소 생명공학연구부) ;
  • 변의백 (한국원자력연구원 첨단방사선연구소 생명공학연구부) ;
  • 김좌진 (건양대학교 의과대학) ;
  • 장범수 (한국원자력연구원 첨단방사선연구소 생명공학연구부) ;
  • 박상현 (한국원자력연구원 첨단방사선연구소 생명공학연구부)
  • Received : 2014.12.17
  • Accepted : 2015.04.21
  • Published : 2015.06.30
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Abstract

The objective of this study was to evaluate the anticancer effects of gamma-irradiated apigenin against various human cancer cells. Structural changes were analyzed by high pressure liquid chromatography. Gamma-irradiated apigenin showed a new peak distinguished from the main peak of apigenin (non-irradiated). Cytotoxic effects in human normal cells (HS68) were not observed upon gamma-irradiated and non-irradiated apigenin treatment. However, gamma-irradiated apigenin treatment significantly increased cytotoxicity against non-small lung cancer cells. For apoptosis induction activity tested by Annexin V/PI staining, gamma-irradiated apigenin showed a stronger effect than non-irradiated apigenin, and the level of reactive oxygen species was apparently elevated by gamma-irradiated apigenin treatment. These results suggest that gamma irradiation could be an effective method for development of a new physiological compound from an original compound by inducing structural changes.

본 연구는 감마선 조사에 의해 유도된 apigenin 화합물(radiolysis products)이 인체유래 다양한 암세포에 처리했을 때의 항암 효과를 알아보기 위하여 실험을 진행하였다. Apigenin을 50 kGy로 조사할 경우 유도 화합물이 생성됨을 확인할 수 있었으며, radiolysis 화합물을 분획하여 인체유래 섬유육종세포(HS68)에 대한 독성을 평가한 결과 독성이 없는 것으로 나타났다. 다양한 암세포에 항암 활성을 평가한 결과 폐암(H1975)세포주의 경우 다른 암세포에 비해 효과가 높은 것으로 나타났다. Annexin V/PI 염색을 통해 감마선 조사된 apigenin 처리구에서 apoptosis의 발현을 확인할 수 있었으며, ROS(reactive oxygen species) 평가 결과에서도 농도 의존적으로 발현을 확인할 수 있었다. 본 연구는 방사선 구조 변환 연구를 통해 방사선을 이용한 새로운 신약 개발 가능성을 제시하는 기초자료로 활용될 수 있을 것으로 판단하였다.

Keywords

References

  1. Kim EY, Kim AK. 2011. Enhancement of TRAIL-induced apoptosis in human hepatocellular carcinoma cells by apigenin. Yakhak Hoeji 55: 49-55.
  2. National Cancer Information Center. 2013. Cancer incidence rate. http://www.cancer.go.kr/mbs/cancer/subview.jsp?id=cancer_040101000000 (accessed Sep 2014).
  3. Statistics Korea. 2014. Causes of death statistics in Korea, 2012. http://www.index.go.kr/potal/main/EachDtlPageDetail.do?idx_cd=2770 (accessed Feb 2015).
  4. Kim SS. 1998. A study on the related factors of Korean cancer-outbreaks. J Korean Soc Health Statistics 23: 1-16.
  5. Mclntire SN, Cioppa AL. 1984. Cancer nursing: A developmental approach. Wiley, New York, NY, USA. p 557-571.
  6. Kuhnau J. 1976. The flavonoids. A class of semi-essential food components: Their role in human nutrition. World Rev Nutr Diet 24: 117-191. https://doi.org/10.1159/000399407
  7. Rhim TJ, Choi MY. 2011. The antioxidative effects of Rhododendron brachycarpum extracts. Korean J Plant Res 24:456-460. https://doi.org/10.7732/kjpr.2011.24.4.456
  8. Yoon JA, Hahm SW, Park J, Son YS. 2009. Total polyphenol and flavonoid of fruit extract of Opuntia humifusa and its inhibitory effect on the growth of MCF-7 human breast cancer cells. J Korean Soc Food Sci Nutr 38: 1679-1684. https://doi.org/10.3746/jkfn.2009.38.12.1679
  9. Peterson J, Dwyer J. 1998. Flavonoids: Dietary occurrence and biochemical activity. Nutr Res 18: 1995-2018. https://doi.org/10.1016/S0271-5317(98)00169-9
  10. Li RR, Pang LL, Du Q, Shi Y, Dai WJ, Yin KS. 2010. Apigenin inhibits allergen-induced airway inflammation and switches immune response in a murine model of asthma. Immunopharmacol Immunotoxicol 32: 364-370. https://doi.org/10.3109/08923970903420566
  11. Shukla S, Gupta S. 2010. Apigenin: A promising molecule for cancer prevention. Pharm Res 27: 962-978. https://doi.org/10.1007/s11095-010-0089-7
  12. Long X, Fan M, Bigsby RM, Nephew KP. 2008. Apigenin inhibits antiestrogen-resistant breast cancer cell growth through estrogen receptor-${\alpha}$ dependent and estrogen receptor-${\alpha}$-independent mechanisms. Mol Cancer Ther 7: 2096-2108. https://doi.org/10.1158/1535-7163.MCT-07-2350
  13. Byun EH, Kim JH, Sung NY, Choi JI, Lim ST, Kim KH, Yook HS, Byun MW, Lee JW. 2008. Effects of gamma irradiation on the physical and structural properties of ${\beta}$- glucan. Radiat Phys Chem 77: 781-786. https://doi.org/10.1016/j.radphyschem.2007.12.008
  14. Kim JK, Sung NY, Srinivasan P, Choi JI, Kim SK, Oh JM, Kim JH, Song BS, Park HJ, Byun MW, Lee JW. 2008. Effect of gamma irradiated hyaluronic acid on acetaminophen induced acute hepatotoxicity. Chem Biol Interact 172: 141-153. https://doi.org/10.1016/j.cbi.2007.11.015
  15. Ananthaswamy HN, Vakil UK, Sreenivasan A. 1970. Effect of gamma radiation on wheat starch and its components. J Food Sci 35: 795-798. https://doi.org/10.1111/j.1365-2621.1970.tb01997.x
  16. Charlesby A. 1981. Crosslinking and degradation of polymers. Radiat Phys Chem 18: 59-66. https://doi.org/10.1016/0146-5724(81)90064-9
  17. Byun MW, Seo JH, Kim JH, Kim MB, Oh NS, Lee JW. 2004. The comparison of a conformational alteration of ovalbumin irradiated with radiation of gamma and electron beam. J Korean Soc Food Sci Nutr 33: 1169-1174. https://doi.org/10.3746/jkfn.2004.33.7.1169
  18. Lee JW, Kim JH, Sung CK, Kang KO, Shin MG, Byun MW. 2000. The changes of allergenic and antigenic properties of major allergen (Pen a 1) of brown shrimp (Penaeus aztecus) by gamma irradiation. Korean J Food Sci Technol 32: 822-827.
  19. Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. 1987. Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Res 47: 936-942.
  20. LeBel CP, Ischiropoulos H, Bondy SC. 1992. Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5: 227-231. https://doi.org/10.1021/tx00026a012
  21. Sung NY, Byun EB, Song DS, Jin YB, Park JN, Kim JK, Park JH, Song BS, Park SH, Lee JW, Kim JH. 2014. Antiinflammatory action of γ-irradiated genistein in murine peritoneal macrophage. Radiat Phys Chem 105: 17-21. https://doi.org/10.1016/j.radphyschem.2014.05.029
  22. Jung HJ, Park HR, Jung U, Jo SK. 2009. Radiolysis study of genistein in methanolic solution. Radiat Phys Chem 78:386-393. https://doi.org/10.1016/j.radphyschem.2009.03.004
  23. Wang C, Kuzer MS. 1997. Phytoestrogen concentration determines effects on DNA synthesis in human breast cancer cells. Nutr Cancer 28: 236-247. https://doi.org/10.1080/01635589709514582
  24. Wang W, Heideman L, Chung CS, Pelling JC, Koehler KJ, Birt DF. 2000. Cell-cycle arrest at G2/M and growth inhibition by apigenin in human colon carcinoma cell lines. Mol Carcinog 28: 102-110. https://doi.org/10.1002/1098-2744(200006)28:2<102::AID-MC6>3.0.CO;2-2
  25. Cutler RG, Plummer J, Chowdhury K, Heward C. 2005. Oxidative stress profiling: Part II. Theory, technology, and practice. Ann N Y Acad Sci 1055: 136-158. https://doi.org/10.1196/annals.1323.031
  26. Moungjaroen J, Nimmannit U, Callery PS, Wang L, Azad N, Lipipun V, Chanvorachote P, Rojanasakul Y. 2006. Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation. J Pharmacol Exp Ther 319: 1062-1069. https://doi.org/10.1124/jpet.106.110965

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