ACOMS+ 및 학술지 리포지터리 설명회

  • 한국과학기술정보연구원(KISTI) 서울분원 대회의실(별관 3층)
  • 2024년 07월 03일(수) 13:30
 

논문 상세

Home > 논문 상세
  • P-ISSN 1010-0695
  • E-ISSN 2288-3339

와송이 인간 백혈병 세포주 THP-1에서 NF-κB 활성 억제와 p38 활성을 통해 세포사멸과 자가포식에 미치는 영향

Effect of Orostachys japonicus on Apoptosis and Autophagy in Human monocytic leukemia Cell line THP-1 via Inhibition of NF-κB and Phosphorylation of p38 MAPK

대한한의학회지 / Journal of Korean Medicine, (P)1010-0695; (E)2288-3339
2019, v.40 no.2, pp.35-50
https://doi.org/10.13048/jkm.19015
주성희 (경희대학교 한의과대학 간계내과교실)
장은경 (경희대학교 한의과대학 간계내과교실)
김영철 (경희대학교 한의과대학 간계내과교실)
  • 다운로드 수
  • 조회수

Abstract

Objectives: Orostachys japonicas (O. japonicus) has been known for its anti-tumor effect. In the present study, it was investigated whether O. japonicus EtOH extracts could induce apoptosis and autophagy which are part of the main mechanism related to anti-tumor effect in THP-1 cells. Methods: Cells were treated with various concentrations of O. japonicus EtOH extracts (0-300μg/ml) for 24, 48, and 72h. Cell viability was evaluated by MTS/PMS assay and apoptosis rate was examined by flow cytometry and ELISA assay. The mRNA expression of apoptosis-related genes (Bcl-2, Mcl-1, Survivin, Bax) and autophagy-related gene (mTOR) was evaluated using real-time PCR. The protein expression of Caspase-3, Akt, LC3Ⅱ, Beclin-1, Atg5, NF-κB, p38, ERK was evaluated using western blot analysis. Results: O. japonicus EtOH extracts inhibited cell proliferation and apoptosis rate was increased in both flow cytometry and ELISA assay. Bcl-2, Mcl-1, Survivin (anti-apoptosis factors) mRNA expressions were decreased and Bax (pro-apoptosis factor) mRNA level was increased. mTOR mRNA expressions was decreased and LC3Ⅱ protein expressions was increased. Activation of NF-κB was decreased and phosphorylation of p38 was increased. Conclusion: O. japonicus is regarded to inhibit cell proliferation, to induce apoptosis and to regulate autophagy-related genes in THP-1 cells via NF-κB and p38 MAPK signaling pathway. This suggests O. japonicus could be an effective herb in treating acute myeloid leukemia.

keywords
Orostachys japonicus, THP-1, acute myeloid leukemia, apoptosis, autophagy


참고문헌

1

1. De Kouchkovsky I, Abdul-Hay, M. Acute myeloid leukemia: a comprehensive review and 2016update. Blood cancer journal. 2016;6(7): e441.

2

2. Park EH, Lee H, Won YJ, Ju HY, Oh CM, Ingabire C, et al. Nationwide statistical analysis of myeloid malignancies in Korea: incidence and survival rate from 1999 to 2012. Blood research. 2015;50(4):204-217.

3

3. Lowenberg B, Downing JR, Burnett A. Acute myeloid leukemia. New England Journal of Medicine, 1999;341(14):1051-1062.

4

4. Shah A, Andersson TML, Rachet B, Björkholm M, Lambert PC. Survival and cure of acute myeloid leukaemia in England, 1971‐2006: a population-based study. British journal of haematology. 2013;162(4):509-516.

5

5. Meyers J, Yu Y, Kaye JA, Davis KL. Medicare fee-for-service enrollees with primary acute myeloid leukemia: an analysis of treatment patterns, survival, and healthcare resource utilization and costs. Applied health economics and health policy. 2013;11(3):275-286.

6

6. Ahn DG. Illustrated guide to clinical medicinal herbs. Seoul:Hyun-am-sa. 2012:697-698.

7

7. Ryu DS, Baek GO, Kim EY, Kim KH, Lee DS. Effects of polysaccharides derived from Orostachys Japonicus on induction of cell cycle arrest and apoptotic cell death in human colon cancer cells. BMB reports. 2010;43(11):750-755.

8

8. Shin DY, Lee WS, Jung JH, Hong SH, Park C, Kim HJ, et al. Flavonoids from Orostachys japonicus A. Berger inhibit the invasion of LnCaP prostate carcinoma cells by inactivating Akt and modulating tight junctions. International journal of molecular sciences. 2013;14(9):18407-18420.

9

9. Ryu DS, Lee HS, Lee GS, Lee DS. Effects of the ethylacetate extract of Orostachys japonicus on induction of apoptosis through the p53-mediated signaling pathway in human gastric cancer cells. Biological and Pharmaceutical Bulletin. 2012;35(5):660-665.

10

10. Kim YI, Park SW, Choi IH, Lee JH, Woo HJ, Kim Y. Effect of Orostachys japonicus on cell growth and apoptosis in human hepatic stellate cell line LX2. The American journal of Chinese medicine. 2011;39(03):601-613.

11

11. Koppula S, Yum MJ, Kim JS, Shin GM, Chae YJ, Yoon T, et al. Anti-fibrotic effects of Orostachys japonicus A. Berger (Crassulaceae)on hepatic stellate cells and thioacetamide -induced fibrosis in rats. Nutrition research and practice. 2017;11(6):470-478.

12

12. Lee HS, Ryu DS, Lee GS, Lee DS. Anti-inflammatory effects of dichloromethane fraction from Orostachys japonicus in RAW 264.7 cells: suppression of NF-κB activation and MAPK signaling. Journal of ethnopharmacology. 2012;140(2):271-276.

13

13. Lee HS, Lee GS, Kim SH, Kim HK, Suk DH, Lee DS. Anti-oxidizing effect of the dichloromethane and hexane fractions from Orostachys japonicus in LPS-stimulated RAW 264.7 cells via upregulation of Nrf2 expression and activation of MAPK signaling pathway. BMB reports. 2014;47(2):98.

14

14. Gerl R, Vaux DL. Apoptosis in the development and treatment of cancer. Carcinogenesis. 2005;26(2):263-270.

15

15. Mathew R, Karantza-Wadsworth V, White E. Role of autophagy in cancer. Nature Reviews Cancer. 2007;7(12):961.

16

16. Choi ES, Lee JH. Orostachys japonicus DW and EtOH extracts Induce Apoptosis in Cholangiocarcinoma Cell Line SNU-1079. Journal of Korean Medicine. 2015;36(4):19-34.

17

17. “Korean traditional herbal medicine standard book”, Korea national legal information center. [cited 2018 December 10]. Available from:http://www.law/go.kr/admRulSc.do?tabMenuId =tab107

18

18. Sill H, Olipitz W, Zebisch A, Schulz E, Wölfler A. Therapy‐related myeloid neoplasms: pathobiology and clinical characteristics. British journal of pharmacology. 2011;162(4):792-805.

19

19. Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453-474.

20

20. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 2009;114(5):937-951.

21

21. Löwenberg, B, Zittoun R, Kerkhofs H, Jehn U, Abels J, Debusscher L, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. Journal of Clinical Oncology. 1989;7(9):1268-1274.

22

22. Cho CS, Cho JG. A literature review of Orostachys japonicus. Collection of dissertations from Korean Medicine Laboratory. 1994;2(2):83-98.

23

23. Lee GS, Lee HS, Kim SH, Suk DH, Ryu DS, Lee DS. Anti-cancer activity of the ethylacetate fraction from Orostachys japonicus for modulation of the signaling pathway in HepG2human hepatoma cells. Food Science and Biotechnology. 2014;23(1):269-275.

24

24. Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase-AKT pathway in human cancer. Nature Reviews Cancer. 2002;2(7):489.

25

25. Shin DY, Lee WS, Jung JH, Hong SH, Park C, Kim HJ, et al. Flavonoids from Orostachys japonicus A. Berger inhibit the invasion of LnCaP prostate carcinoma cells by inactivating Akt and modulating tight junctions. International journal of molecular sciences. 2013;14(9):18407-18420.

26

26. Jung CH, Ro SH, Cao J, Otto NM, Kim DH. mTOR regulation of autophagy. FEBS letters. 2010;584(7):1287-1295.

27

27. Tanida I, Ueno T, Kominami E. LC3 and Autophagy. In Autophagosome and Phagosome. Humana press. 2008;77-88.

28

28. Kang R, Zeh H, Lotze M, Tang D. The Beclin 1 network regulates autophagy and apoptosis. Cell death and differentiation. 2011;18(4):571.

29

29. Codogno P, Meijer AJ. Atg5: more than an autophagy factor. Nature cell biology. 2006;8(10):1045.

30

30. Kim A, Yim NH, Ma JY. Samsoeum, a traditional herbal medicine, elicits apoptotic and autophagic cell death by inhibiting Akt/mTOR and activating the JNK pathway in cancer cells. BMC complementary and alternative medicine. 2013;13(1):233.

31

31. Reed JC. Apoptosis-targeted therapies for cancer. Cancer cell. 2003;3(1):17-22.

32

32. Murphy LO, Blenis J. MAPK signal specificity:the right place at the right time. Trends in biochemical sciences. 2006;31(5):268-275.

상단으로 이동

대한한의학회지