Food Science and Biotechnology

Korean Society of Food Science and Technology (한국식품과학회)
권호 표지

Induction of Cytotoxicity and Apoptosis in HT-29 Human Colon Carcinoma Cells by a Gleditsiae Semen Extract

  • Cha, Mi-Ran (Department of Food Science and Biotechnology, Kyungnam University) ;
  • Kim, Ju-Young (Department of Food Science and Biotechnology, Kyungnam University) ;
  • Hwang, Ji-Hwan (Department of Food Science and Biotechnology, Kyungnam University) ;
  • Park, Hae-Ryong (Department of Food Science and Biotechnology, Kyungnam University)
  • Published : 2007.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Gleditsiae Semen (GS) has been used in both Korea and China as herbal medicine for the treatment of cephalalgia, catharsis, and other diseases. However, the apoptosis of GS against human cancer cells has not previously been investigated. The primary objective of this study was to determine the mechanisms inherent in GS-induced cytotoxicity and apoptosis, using methanolic extract of GS (GSE) in HT-29 human colon carcinoma cells. We found that GSE induced cytotoxicity in HT-29 cells in a dose-dependent manner, and this effect was verified via a lactate dehydrogenase release assay and a colony formation assay. In particular, HT-29 cells showed extensive cell death when treated with $50\;{\mu}g/mL$ of GSE; the calculated $IC_{50}$ value was $20\;{\mu}g/mL$. It induced characteristic apoptotic signs in HT-29 cells, including chromatin condensation and DNA fragmentation, occurring within 6-24 hr when the cells were treated at a concentration of $50\;{\mu}g/mL$. Interestingly, we detected the activation of caspase-3 and -9, but not caspase-8, and apoptotic bodies in GSE-treated HT-29 cells. Collectively, our results indicate that GSE induces apoptosis via a mitochondria-mediated apoptotic pathway, and these findings may be significant with regard to the development of a new drug for the treatment of human colon carcinoma cells.

Keywords

References

  1. Kozlenko M, Vol A, Zusman I. Stability-variability conflict as a reason for cancer: Physical and social aspects. Med. Hypotheses 57: 648-654 (2001) https://doi.org/10.1054/mehy.2001.1434
  2. Chattopadhyay S, Bisaria VS, Panda AK, Srivastava AK. Cytotoxicity of in vitro produced Podophyllotoxin from Podophyllum hexandrum on human cancer cell line. Nat. Prod. Res. 18: 51-57 (2004) https://doi.org/10.1080/1057563031000122095
  3. Lee YS, Yang HO, Shin KH, Choi HS, Jung SH, Kim YM, Oh DK, Linhardt RJ, Kim YS. Suppression of tumor growth by a new glycosaminoglycan isolated from the African giant snail Achatina fulica. Eur. J. Pharmacol. 465: 191-198 (2003) https://doi.org/10.1016/S0014-2999(03)01458-4
  4. Axelson H, Fredlund E, Ovenberger M, Landberg G, Pahlman S. Hypoxia-induced dedifferentiation of tumor cells - A mechanism behind heterogeneity and aggressiveness of solid tumors. Semin. Cell Dev. Biol. 16: 554-563 (2005) https://doi.org/10.1016/j.semcdb.2005.03.007
  5. Vaupel P, Yhews O, Hoeckel M. Treatment resistance of solid tumors: role of hypoxia and anemia. Med. Oncol. 18: 243-259 (2001) https://doi.org/10.1385/MO:18:4:243
  6. Yu Z, Li W. Induction of apoptosis by puerarin in colon HT-29 cells. Cancer Lett. 238: 53-60 (2006) https://doi.org/10.1016/j.canlet.2005.06.022
  7. Park HR, Tomida A, Sato S, Tsukumo Y, Yun J, Yamori T, Hayakawa Y, Tsuruo T, Shin-ya K. Effect on tumor cells of blocking survival response to glucose deprivation. J. Natl. Cancer J. 96: 1300-1310 (2004) https://doi.org/10.1093/jnci/djh243
  8. Chen T, Pengetnze Y, Taylor CC. Src inhibition enhances paclitaxel cytotoxicity in ovarian cancer cells by caspase-9-independent activation of caspase-3. Mol. Cancer Ther. 4: 217-224 (2005)
  9. Rhoo IJ, Park HR, Choo SJ, Hwang JH, Park YM, Bae KH, Shin-ya K, Yoo ID. Selective cytotoxic activity of valinomycin against HT29 human colon carcinoma cells via down-regulation of GRP78. Biol. Pharm. Bull. 29: 817-820 (2006) https://doi.org/10.1248/bpb.29.817
  10. Sausville EA. Versipelostatin: Unfolding an unsweetened death. J. Natl. Cancer I. 96: 1266-1267 (2004) https://doi.org/10.1093/jnci/djh276
  11. Lim SM, Lee GJ, Park SM, Ahn DH, Im DS. Chracterization of Lactobacillus cellobiosus D37 isolated from soybean paste as a probiotic with anticancer and antimicrobial properties. Food Sci. Biotechnol. 15: 792-798 (2006)
  12. Rao A, Cohen HJ. Symptom management in the elderly cancer patient: fatigue, pain, and depression. J. Natl. Cancer I. Monogr. 32: 150-157 (2004)
  13. Davis MP, Walsh D. Treatment of nausea and vomiting in advanced cancer. Support Care Cancer 8: 444-452 (2000) https://doi.org/10.1007/s005200000151
  14. Marx J. Cancer research. Preventing hair loss from chemotherapy. Science 291: 25-26 (2001)
  15. Gorlick R, Bertino JR. Drug resistance in colon cancer. Semin. Oncol. 26: 606-611 (1999)
  16. Serova M, Calvo F, Lokiec F, Koeppel F, Poindessous V, Larsen AK, Laar ESV, Waters SJ, Cvitkovic E, Raymond E. Characterizations of irofulven cytotoxicity in combination with cisplatin and oxaliplatin in human colon, breast, and ovarian cancer cells. Cancer Chemoth. Pharm. 57: 491-499 (2006) https://doi.org/10.1007/s00280-005-0063-y
  17. Gouaze V, Yu JY, Bleicher RJ, Han TY, Liu YY, Wang H, Gottesman MM, Bitterman A, Giuliano AE, Cabot MC. Over expression of glucosylcerarnide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy. Mol. Cancer Ther. 3: 633-639 (2004)
  18. Oh CH, Kang PS, Kim JW, Kwon J, Oh SH. Water extracts of cultured mountain ginseng stimulate immune cells and inhibit cancer cell proliferation. Food Sci. Biotechnol. 15: 369-373 (2006)
  19. Kodach LL, Bos CL, Duran N, Peppelenbosch MP, Ferreira CV, Hardwick JCH. Violacein synergistically increases 5-fluorouracil cytotoxicity, induces apoptosis, and inhibits Akt-mediated signal transduction in human colorectal cancer cells. Carcinogenesis 27: 508-516 (2006) https://doi.org/10.1093/carcin/bgi307
  20. Cha MR, Yoon MY, Kim JY, Hwang JH, Park HR. The cytotoxic effect of the Gleditsiae Semen extracts on human colon carcinoma cells. J. Korean Soc. Appl. Biol. Chem. 49: 248-253 (2006)
  21. Lim JC, Park JH, Budesinsky M, Kasal A, Ran YH, Koo BS, Lee SI, Lee DU. Antimutagenic constituents from the thorns of Gleditsia sinensis. Chem. Pharm. Bull. 53: 561-564 (2005) https://doi.org/10.1248/cpb.53.561
  22. Chow LM, Tang JC, Teo IT, Chui CH, Lau FY, Leung TW, Cheng G, Wong RS, Wong IL, Tsang KM, Tan WQ, Zhao YZ, Lai KB, Lam WH, Guo DA, Chan AS. Antiproliferative activity of the extract of Gleditsia sinensis fruit on human solid tumour cell lines. Chemotherapy 48: 303-308 (2002) https://doi.org/10.1159/000069713
  23. Cheung F, Chui CH, Chan AS, Lau FY, Cheng GY, Wong RS, Kok SH, Teo IT, Cheng CH, Tang JC. Inhibition of proteasome activity Gleditsia sinensis fruit extract-mediated apoptosis on human carcinoma cells. Int. J. Mol. Med. 16: 925-929 (2005)
  24. Konoshima T, Yasuda I, Kashiwada Y, Cosentino LM, Lee KH. Anti-AIDS agents, 21. Triterpenoid saponins as anti-HIV principles from fruits of Gleditsia japonica and Gymnocladus chinensis, and a structure-activity correlation. J. Nat. Prod. 58: 1372-1377 (1995) https://doi.org/10.1021/np50123a006
  25. Schlosser SF, Azzaroli F, Dao T, Hingorani R, Crispe IN, Boyer JL. Induction of murine hepatocyte death by membrane-bound CD95 (Fas/APO-1)-ligand: characterization of an in vitro system. Hepatology 32: 779-785 (2000) https://doi.org/10.1053/jhep.2000.18422
  26. Choi HJ, Yee SB, Park SE, Im E, Jung JH, Chung HY, Choi YH, Kim ND. Petrotetrayndiol A induces cell cycle arrest and apoptosis in SK-MEL-2 human melanoma cells through cytochrome cmediated activation of caspases. Cancer Lett. 232: 214-225 (2006) https://doi.org/10.1016/j.canlet.2005.02.030
  27. Zhu W, Masaki T, Cheung AK, Kern SE. Cellular pharmacokinetics and pharmacodynamics of dipyridamole in vascular smooth muscle cells. Biochem. Pharmacol. 72: 956-964 (2006) https://doi.org/10.1016/j.bcp.2006.07.027
  28. Cha JD, Jeong MR, Lee YE. Induction of apoptosis in human oral epidermoid carcinoma cells by essential oil of Chrysanthemum boreale Makino. Food Sci. Biotechnol. 14: 350-354 (2005)
  29. Ogiso Y, Tomida A, Lei S, Omura S, Tsuruo T. Proteasome inhibition circumvents solid tumor resistance to topoisomerase IIdirected drugs. Cancer Res. 60: 2429-2434 (2000)
  30. Kim HJ, Park HJ, Park WS, Bae Y. CD43 cross-linking increases the Fas-induced apoptosis through induction of Fas aggregation in Jurkat T-cells. Exp. Mol. Med. 38: 357-363 (2006) https://doi.org/10.1038/emm.2006.42
  31. Lee H, Kim YJ, Kim HW, Lee DH, Sung MK, Park T. Induction of apoptosis by Cordyceps militaris through activation of caspase-3 in leukemia HL-60 cells. Biol. Pharm. Bull. 29: 670-674 (2006) https://doi.org/10.1248/bpb.29.670