ANTICANCER EFFECTS OF CAESALPINIA SAPPAN EXTRACTS ON ORAL CARCINOMA AND OSTEOSARCOMA CELLS

소목 추출물의 구강암 및 골육종 세포주에 대한 항암작용에 관한 연구

  • Lee, Jong-Su (Dept. of Oral Maxillofacial Surgery, School of Dentistry, Kyung Hee University) ;
  • Kim, Jeong-Hee (Dept. of Oral Biochemistry, School of Dentistry and Institute of Oral Biology, KyungHee University) ;
  • Kim, Yeo-Gab (Dept. of Oral Maxillofacial Surgery, School of Dentistry, Kyung Hee University)
  • 이종수 (경희대학교 치과대학 치의학과 구강악안면외과학교실) ;
  • 김정희 (경희대학교 치과대학 치의학과 구강생화학교실 및 구강생물학연구소) ;
  • 김여갑 (경희대학교 치과대학 치의학과 구강악안면외과학교실)
  • Published : 2007.12.31

Abstract

Anticancer effect of methanol extract of Caesalpinia sappan L. on oral carcinoma(KB) and osteosarcoma(HOS) cells were investigated in this study. In order to elucidate the anticancer mechanism of Caesalpinia sappan L, we analyzed telomerase inhibitory effect of the methanol extract of Caesalpinia sappan L. In addition, we prepared 5 fraction samples according to its polarity differences and analyzed anticancer effects on oral carcinoma and osteosarcoma cells. Following results are obtained in this study. 1. 50% cell proliferation inhibitory value($IC_{50}$) of the methanol extract of Caesalpinia sappan L. against oral carcinoma(KB) cells and osteosarco ma(HOS) cells were $9.0{\mu}g/ml\;and\;10.9{\mu}g/ml$, respectively. 2. The methanol extract of Caesalpinia sappan L. showed inhibitory effect of telomerase which is required for cancer cell immortality. Therefore, it seems that the anticancer effect of methanol extract of Caesalpinia sappan is at least partially due to telomerase inhibitory effect. 3. Five fraction samples were prepared according to its polarity and 88.7% of ingredient of total methanol extract was transferred to ethylacetate fraction. Thin layer chromatography analysis showed that dichloromethane fraction contained ingredient with relatively high polarity and ethylacetate fraction contained similar ingredient found in total methanol extract. 4. Anticancer effect was observed in n-hexane, dichloromethane, and ethylacetate fractions. The highest anticancer effect was found in dichloromethane fraction which had $IC_{50}$ value of $4.4{\mu}g/ml$ and > $4.0{\mu}g/ml$ against oral carcinoma(KB) cells and osteosarcoma(HOS) cells, respectively.

Keywords

References

  1. Silverman S, Gorsky M: Epidemiologic and demographic update in oral cancer: California and national data-1973 to 1985. J Am Dent Assoc 1990;120:495-499 https://doi.org/10.14219/jada.archive.1990.0082
  2. Lee SC, Kim YG. Oral and Maxillofacial Oncology. Seoul, Jisung. 1993
  3. Kish JA, Weaver A, Jacobs J, Cummings G, Al-Sarraf M: Cisplatin and 5-fluorouracil infusion in patients with recurrent and disseminated epidermoid cancer of the head and neck. Cancer 1984;53:1819-1824 https://doi.org/10.1002/1097-0142(19840501)53:9<1819::AID-CNCR2820530903>3.0.CO;2-R
  4. Al-Sarraf M, Pajak TF, Marcial VA, Mowry P, Cooper JS, Stetz J, Ensley JF, Velez-Garcia E: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG study. Cancer 1987;59:259-265 https://doi.org/10.1002/1097-0142(19870115)59:2<259::AID-CNCR2820590214>3.0.CO;2-1
  5. Lee JH, Kim MJ: Chemosensitivity of cisplatin and 5-fluorouracil on oral squamous cell carcinoma cell lines. J Kor Assoc Oral Maxillofac Surg 1998;24:165-171
  6. Peterson LJ, Indresano AT, Marciani RD, Roser SM. Principles of oral and maxillofacial surgery. Philadelphia, J.B.Lippincott. 1992
  7. Lee YY, You KH, Kim SY, Ahn BZ: Augmentation of the cytotoxic effects of anticancer drugs by (${\pm}$)-ar-turmerone and extracts of the lithosperma and scutellaria roots against human leukemia cell lines. Yakhak Hoeji 1991;35:203-215
  8. Lee YH, Kim YG, Kim JH: Studies on anti-oral cancer activities of medicinal plant extracts. J Kor Assoc Oral Maxillofac Surg 2000;26:53-58
  9. Lee JS, Kim JH, Kim YG: Studies on the effects of ginseng saponins on oral cancer and normal cells. Kyung Hee Dental J 1998;20:117-128
  10. Bomser J, Madhavi DL, Singletary K, Smith MAL: In vitro anticancer activity of fruit extracts from Vaccinium species. Planta Med 1996;62:212-216 https://doi.org/10.1055/s-2006-957862
  11. Wickramaratne DBM, Mar W, Chai H, Castillo JJ, Farnsworth NR, Soejarto DD, Cordell GA, Pezzuto JM, Kinghorn AD: Cytotoxic constituents of Bursera permollis. Planta Med 1995;61:80-81 https://doi.org/10.1055/s-2006-958008
  12. Mallery SR, Stoner GD, Larsen PE, Fields HW, Rodrigo KA, Schwartz SJ, Tian Q, Dai J, Mumper RJ: Formulation and in-vitro and in-vivo evaluation of a mucoadhesive gel containing freeze dried black raspberries: implications for oral cancer chemoprevention. Pharm Res 2007;24:728-737 https://doi.org/10.1007/s11095-006-9192-1
  13. Manoharan S, Kavitha K, Senthil N, Renju GL: Evaluation of anticarcinogenic effects of clerodendron inerme on 7,12-dimethylbenz(a) anthracene-induced hamster buccal pouch carcinogenesis. Singapore Med J 2006;47:1038-1043
  14. Kim JH, Lee SJ, Han YB, Kim JB: Identification of active component isolated from Croton tiglium and Coptis japonica aqueous mixture (CP2) and studies of its cytotoxic effect. Yakhak Hoeji 1994;38:31-37
  15. Konkimalla VB, Suhas VL, Chandra NR, Gebhart E, Efferth T: Diagnosis and therapy of oral squamous cell carcinoa. Expert Rev Anticancer Ther 2007;7:317-329 https://doi.org/10.1586/14737140.7.3.317
  16. Pezzuto JM: Plant-derived anticancer agents. Biochem Pharmcol 1997;53:121-133 https://doi.org/10.1016/S0006-2952(96)00654-5
  17. Saitoh T, Sakashita S, Nakata H, Shimokawa T, Kinjo JE, Yamahara J, Yamasaki M, Nohara T: 3-Benzylchroman derivatives related to brazilin from Sappan Lignum. Chem Pharm Bull 1986;34:2506-2511 https://doi.org/10.1248/cpb.34.2506
  18. Namikoshi M, Nakata H, Yamada H, Nagai M, Saitoh T: Homoisoflavonoids and related compounds. II. Isolation and absolute configuration of 3, 4-dihydroxylated homoisoflavans and brazilins from Caesalpinia sappan L. Chem Pharm Bull 1987;35: 2761-2773 https://doi.org/10.1248/cpb.35.2761
  19. Baek NI, Jeon SG, Ahn EM, Hahn JT, Bahn JH, Jang JS, Cho SW, Park JK, Choi SY: Anticonvulsant compounds from the wood of Caesalpinia sappan L. Arch Pharm Res 2000;23:344-348 https://doi.org/10.1007/BF02975445
  20. Xie YW, Ming DS, Xu HX, Dong H, But PP: Vasorelaxing effects of Caesalpinia sappan involvement of endogenous nitric oxide. Life Sci 2000;67:1913-1918 https://doi.org/10.1016/S0024-3205(00)00772-4
  21. Oh SR, Kim DS, Lee IS, Jung KY, Lee JJ, Lee HK: Anticomplementary activity of constituents from the heartwood of Caesalpinia sappan. Planta Med 1998;64:456-458 https://doi.org/10.1055/s-2006-957481
  22. Choi SY, Yang KM, Jeon SD, Kim JH, Khil LY, Chang TS, Moon CK: Brazilin modulates immune function mainly by augmenting T cell activity in halothane administered mice. Planta Med 1997;63:405-408 https://doi.org/10.1055/s-2006-957722
  23. Moon CK, Park KS, Kim SG, Won HS, Chung JH: Brazilin protects cultured rat hepatocytes from BrCCl3-induced toxicity. Drug Chem Toxicol 1992;15:81-91 https://doi.org/10.3109/01480549209035174
  24. Hikino H, Taguchi T, Fujimura H, Hiramatsu Y: Antiinflammatory principles of Caesalpinia sappan wood and of Haematoxylon campechianum wood. Planta Med 1977;31:214-220 https://doi.org/10.1055/s-0028-1097516
  25. Blackburn EH. Structure and function of telomeres. Nature 1991;350:569-573 https://doi.org/10.1038/350569a0
  26. Allsopp RC, Vaziri H, Patterson C, Goldstein S, Younglai EV, Futcher AB, Greider CW, Harley CB: Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 1992;89:10114-10118
  27. Harley CB, Kim NW. Telomerase and cancer. Important Advances in Oncolology. Philadelphia, Lippincott-Raven Publishers. 1996:57-67
  28. Harley CB, Villeponteau B: Telomeres and telomerase in aging and cancer. Curr Opin Genet Dev 1995;5:249-255 https://doi.org/10.1016/0959-437X(95)80016-6
  29. Rhyu MS: Telomeres, telomerase, and immortality. J Natl Cancer Inst 1995;87:884-894 https://doi.org/10.1093/jnci/87.12.884
  30. Greider CW, Blackburn EH: Telomeres, telomerase and cancer. Sci Am 1996;274:92-97 https://doi.org/10.1038/scientificamerican0296-92
  31. Shay JW, Wervin H, Wright WE: Telomere shortening may contribute to aging and cancer: a perspective. Mol Cell Diff 1994;2:1-21
  32. Miyoshi Y, Tsukinoki K, Imaizumi T, Yamada Y, Ishizaki T, Watanabe Y, Sasakura Y, Lin Y, Hosaka M, Kubota Y: Telomerase activity in oral cancer. Oral Oncology 1999;35:283-289 https://doi.org/10.1016/S1368-8375(98)00117-1
  33. Mutirangura A, Supiyaphun P, Trirekapan S, Sriuranpong V, Sakuntabhai A, Yenrudi S, Voravud N: Telomerase activity in oral leukoplakia and head and neck squamous cell carcinoma. Cancer Research 1996;56:3530-3533
  34. Zimmermann S, Martens UM: Telomeres and telomerase as targets for cancer therapy. Cell Mol Life Sci 2007;64:906-921 https://doi.org/10.1007/s00018-007-6481-8
  35. Kelland LR: Overcoming the immortality of tumour cells by telomere and telomerase based cancer therapeutics--current status and future prospects. 2005;41:971-979 https://doi.org/10.1016/j.ejca.2004.11.024
  36. Olaussen KA, Dubrana K, Domont J, Spano JP, Sabatier L, Soria JC: Telomere and telomerase as targets for anticancer drug development. 2006;57:191-214 https://doi.org/10.1016/j.critrevonc.2005.08.007
  37. Hansen MB, Nielsen SE, Berg K: Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods 1989;119:203-210 https://doi.org/10.1016/0022-1759(89)90397-9
  38. Kim NW, Piatysyzek, MA, Prowse KR, Harley CB, West MD, Ho PLC Coviello GM, Wright WE, Weinrich SL, Shay JW: Specific association of human telomerase activity with immortal cells and cancer. Science 1994;266:2011-2015 https://doi.org/10.1126/science.7605428
  39. Park JG, Hyun JW, Lim KH, Shin JE, Won YJ, Yi YD, Shin KH, Chang IM, Woo WS: Antineoplastic effect of extracts from traditional medicinal plants. Kor J Pharmacognosy 1993;24:223-230
  40. Yang YM, Hyun JW, Lim KH, Sung MS, Kang SS, Paik WH, Bae KW, Cho H, Kim HJ, Woo ER, Park H, Park JG: Antineoplastic effect of extracts from traditional medicinal plants and various plants (III). Kor J Pharmacognosy 1996;27:105-110
  41. Meyers EN, Suen JY. Cancer of the head and neck 2nd ed. NewYork, Churchill Livingstone. 1989
  42. Weaver A, Flemming S, Kish J, Vandenberg H, Jacob J, Crissman J, Al-Warraf M: cisplatin and 5-fluorouracil as induction therapy for advanced head and neck cancer. Am J Surg 1982;144:445-448 https://doi.org/10.1016/0002-9610(82)90419-6
  43. Watson J: Origin of concatemeric T7 DNA. Nature New Biol 1972;239:197 https://doi.org/10.1038/239197a0
  44. Makarov VL, Hirose Y, Langmore JP: Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 1997;88:657-666 https://doi.org/10.1016/S0092-8674(00)81908-X
  45. Wong DTW, Todd R, Tsuji T, Donoff RB: Molecular biology of human oral cancer. Crit Rev Oral Biol Med 1996;7:319-328 https://doi.org/10.1177/10454411960070040201
  46. Suto A, Kubota J, Shimoyama Y: MTT assay with reference to the clinical effect of chemosensitivity. J Surg Oncol 1989;42:28-32 https://doi.org/10.1002/jso.2930420108