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영남의대학술지 Vol.24_No.2 Suppl. P.S580-590, Dec. 2007

Original Article

사람 유방암세포들에서 Gleditsin의 항암효과

Anticancer Effects of Gleditsin in Human Mammary Cancer Cells

고현숙, 강경원, 김정희
영남대학교 의과대학 생화학ㆍ분자생물학교실
책임저자:김정희, 대구광역시 남구 대명동 317-1, 영남대학교 의과대학 생화학·분자생물학교실
Tel: (053) 620-4341, Fax: (053) 654-6651
E-mail: jhykim@ynu.ac.kr

December 30, 2007

Abstract

Background:Gleditsin is a herb medicine from extracted by Gleditschia spina. In oder to investigate anticancer effects of gleditsin in human various breast cancer cells, we tested with gleditsin on cytotoxicity of materials, observed to cell survival and cell cycle progression, and analyzed in starvation condition.
Materials and Methods:The cytoxicity and cell cycle progression were analyzed in human breast cells, MCF-10A and human breast cancer cell lines, MDA-MB-231, MDA-MB-361, and MDA-MB-435. IC50s of breast cancer cell lines were measured by MTT assay. The cell cycle were showed by flow cytometric analysis in cells treated with gleditsin. We analyzed DNA content of sub-Go/G1 phase, it was detected apoptosis.
Results:Cell survivals were decreased in a dose-dependent manner by the treatment of cells with gleditsin. IC50s were 4.11-fold higher in MDA-MB-435, 2.53-fold higher in MDA- MB-231, and 2.55-fold higher in MDA-MB-361 than in normal breast cells. Flow cytometric analysis showed that sub-G0/G1 fractions in cancer cells treated with gleditsin were higher than that normal cells, suggesting that increases in cytotoxicity of cancer cells by gleditsin were resulted from apoptosis. Cell cycle progression was also changed by the treatment of gleditsin. The treatments of gleditsin resulted in a decrease in G1 phase and an increase in G2/M phase in normal breast cells as well as cancer cell lines. Apoptotic cell death was synergistically increased by cell starvation and gleditsin treatments in cancer cells. MDA- MB-435 cells were more sensitive to apoptotic cell death by gleditsin than other cells.
Conclusion:An anti-tumor effect of gleditsin was selectively higher in hman breast cancer cells than in normal human breast cells, and was mediated by apoptotic cell death.

Key Words: Gleditsin, Apoptosis, Cell Cycle Progression

References

1. 정재동외 2명 공저. 생물공학(Plant Biotechnology) 경북대학교출판부 1992.

2. 남상윤. Sarcoma-180 암세포를 이식한 마우스에서 lymphokine-activated killer 세포활성의 변화. 단국대학교 대학원 박사학위논문집 1991.

3. 하재청. Sarcoma-180에 대한 약용식물 성분의 항암효과. 대한암학회지 1991;23:197-205.

4. 전인기, 박성용, 이학수, 김대현, 이광신, 최영태. Effect of Gleditsia spina extract on ascites tomor sarcoma-180 in mice. 동국대학교 이학사학위논문 1994.

5. Berridge MJ. Inositol triphosphate and calcium signalling. Nature 1993;361:315-25.

6. Wahl MT, Nishibe S, Suh PG, Rhee SG, Carpenter G. Epidermal growth factor stimulates tyrosine phosphorylation of phospholipase C-II independently of receptor internalization and extracellular calcium. Proc Natl Acad Sci USA 1989;86:1568-72.

7. Nishibe S, Wahl MI, Wedegaertner PB, Kim JW, Rhee SG, Carpenter G. Selectivity of phospholipase C phosphorylation by the epidermal growth factor receptor, the insulin receptor, and their cytoplasmic domains. Proc Narl Acad Sci USA 1990;87:424-8.

8. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, MercerE, Kinzler KW, Vogelstein B. Waf1, a potential mediator of p53 tumor suppression. Cell 1993; 75:817-25.

9. Levine AJ. The tumor supressor genes. Ann Rev Biochem 1993;62:623-51.

10. Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS-3rd, Johnson BE, Skolnick MHA. A cell cycle regulator potentially involved in genesis of many tumor types. Science 1994; 264:436-40.

11. Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 1995; 9:1149-63.

12. Hunter T, Pines J. Cyclins and cancer II: cyclin D and CDK inhibitors come of age. Cell 1994; 79:181-4.

13. Weinberg RA. The retinoblastoma protein and cell cycle control. Cell 1995;81:323-30.

14. Kamb A. Role of a cell cycle regulator in hereditary and sporadic cancer. Cold Spring Harb Symp Quant Biol 1994;59:39-47.

15. Yeager T, Stadler W, Belair C, Puthenveettil J, Olopade O, Reznikoff C. Increased p16 levels correlate with pRb alterations in human urothelial cells. Cancer Res 1995;55:493-7.

16. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature 1994;368:753-6.

17. Haapajarvi T, Kivinen L, Pitkanen K, Laiho M. Cell cycle dependent effects of u.v.-radiation on p53 expression and retinoblastoma protein phosphorylation. Oncogene 1995;11:151-9.

18. Leonard CJ, Canman CE, Kastam MB. The role of p53 in cell-cycle control and apoptosis: implications for cancer. Important Adv Oncol 1995:33-42.

19. Thomson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995;267: 1456-62.

20. Robbins BA, de la Vega D, Ogata K, Tan EM, Nakamura RM. Immunohistochemical detection of proliferating cell nuclear antigen in solid human malignancies. Arch Pathol Lab Med 1987;111:841-5.

21. Lee YH, Ahn JB, Shin DH, Hong SW, Shim JY, Jung KY, Kim SK, Chang J, Kim JH, Lee WY, Kim BS, Kim SK. Prognostic value of PCNA, c-erbB-2, c-fos in patients with non-small cell lung cancer. J Korean Cancer Assoc 1999;31:678-85.

22. Lim CC, Kim IH, Cho JW, Baek JS, Shon SS. Expression of cell cycle control genes in korean gastric cancer cell lines. J Korean Cancer Assoc 2000;32:279-87.