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Methanolic Extracts of Uncaria rhynchophylla Induce Cytotoxicity and Apoptosis in HT-29 Human Colon Carcinoma Cells

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Abstract

In this paper, we report the anticancer activities of Uncaria rhynchophylla extracts, a Rubiaceae plant native to China. Traditionally, Uncaria rhynchophylla has been used in the prevention and treatment of neurotoxicity. However, the cytotoxic activity of Uncaria rhynchophylla against human colon carcinoma cells has not, until now, been elucidated. We found that the methanolic extract of Uncaria rhynchophylla (URE) have cytotoxic effects on HT-29 cells. The URE showed highly cytotoxic effects via the MTT reduction assay, LDH release assay, and colony formation assay. As expected, URE inhibited the growth of HT-29 cells in a dose-dependent manner. In particular, the methanolic URE of the 500 μg/ml showed 15.8% inhibition against growth of HT-29 cells. It induced characteristic apoptotic effects in HT-29 cells, including chromatin condensation and sharking occurring 24 h when the cells were treated at a concentration of the 500 μg/ml. The activation of caspase-3 and the specific proteolytic cleavage of poly (ADP-ribose) polymerase were detected over the course of apoptosis induction. These results indicate that URE contains bioactive materials with strong activity, and is a potential chemotherapeutic agent candidate against HT-29 human colon carcinoma cells.

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Abbreviations

DMSO:

dimethyl sulfoxide

LDH:

lactate dehydrogenase

MTT:

3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide

URE:

methanolic extract of Uncaria rhynchophylla

References

  1. Lee LL, Jannapureddy M, Albo D, Awad SS, Farrow B, Bellows CC, Berger DH (2007) Outcomes of veterans affairs patients older than age 80 after surgical procedures for colon malignancies. Am J Surg 194:646–651

    Article  Google Scholar 

  2. Lowe SW, Lin AW (2000) Apoptosis in cancer. Carcinogenesis 21:485–495

    Article  CAS  Google Scholar 

  3. Chatelut E, Delord JP, Canal P (2003) Toxicity patterns of cytotoxic drugs. Invest New Drugs 21:141–148

    Article  CAS  Google Scholar 

  4. Manoj G, Thampi BSH, Leelamma S, Menon PVG (2001) Effect of dietary fiber on the activity on intestinal and fecal beta-glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis. Plant Foods Hum Nutr 56:13–21

    Article  CAS  Google Scholar 

  5. Lee AS (2001) The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci 26:504–510

    Article  CAS  Google Scholar 

  6. Pohlen U, Mansmann U, Berger G, Germer CT, Gallkowski U, Boese-Landgraf J, Buhr HJ (2004) Multicenter pilot study of 5-fluorouracil, folinic acid, interferon alpha-2b and degradable starch microspheres via hepatic arterial infusion in patients with nonresectable colorectal liver metastases. Anticancer Res 24:3275–3282

    CAS  Google Scholar 

  7. Heys SD, Eremin O, Ruggeri EM, Pein F, Rainer H, Oskam R, de Peuter RA, Palmer PA, Franks CR (1995) A phase III study of recombinant interleukin-2,5-fluorouracil and leucovorin versus 5-fluorouracil and leucovorin in patients with unresectable or metastatic colorectal carcinoma. Eur J Cancer 31:19–25

    Article  Google Scholar 

  8. Tomida A, Tsuruo T (1999) Drug resistance mediated by cellular stress response to the microenvironment of solid tumors. Anticancer Drug Des 14:169–177

    CAS  Google Scholar 

  9. Sausville EA (2004) Versipelostatin: unfolding an unsweetened death. J Natl Cancer Inst 96:1266–1267

    CAS  Google Scholar 

  10. Park HR, Tomida A, Sato S, Tsukumo Y, Yun J, Yamori T, Hayakawa Y, Tsuruo T, Shin-ya K (2004) Effect on tumor cells of blocking survival response to glucose deprivation. J Natl Cancer Inst 96:1300–1310

    Article  CAS  Google Scholar 

  11. Park HR, Ryoo IJ, Choo SJ, Hwang JH, Kim JY, Cha MR, Shin-ya K, Yoo ID (2007) Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator. Toxicology 229:253–261

    Article  CAS  Google Scholar 

  12. Tsuruo T, Naito M, Tomida A, Fujita N, Mashima T, Sakamoto H, Haga N (2003) Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal. Cancer Sci 94:15–21

    Article  CAS  Google Scholar 

  13. Vaux DL, Korsmeyer SJ (1999) Cell death in development. Cell 96:245–254

    Article  CAS  Google Scholar 

  14. Gouaze V, Yu JY, Bleicher RJ, Han TY, Liu YY, Wang H, Gottesman MM, Bitterman A, Giuliano AE, Cabot MC (2004) Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy. Mol Cancer Ther 3:633–639

    CAS  Google Scholar 

  15. Cha MR, Kim JY, Hwang JH, Park HR (2007) Induction of cytotoxicity and apoptosis by Gleditsiae Semen extract in HT-29 human colon carcinoma cells. Food Sci Biotechnol 16:260–264

    Google Scholar 

  16. Lee J, Son D, Lee P, Kim DK, Shin MC, Jang MH, Kim CJ, Kim YS, Kim SY, Kim H (2003) Protective effect of methanol extract of Uncaria rhynchophylla against excitotoxicity induced by N-methyl-d-aspartate in rat hippocampus. J Pharmacol Sci 92:70–73

    Article  CAS  Google Scholar 

  17. Jung JW, Ahn NY, Oh HR, Lee BK, Lee KJ, Kim SY, Cheong JH, Ryu JH (2006) Anxiolytic effects of the aqueous extract of Uncaria rhynchophylla. J Ethnopharmalcol 108:193–197

    Article  Google Scholar 

  18. Hwang JH, Kim JY, Cha MR, Park HR (2007) Effect of methanolic extract from silkworm droppings on proliferation and caspase activity in HT-29 human colon cancer cells. J Med Food 10:467–472

    Article  CAS  Google Scholar 

  19. Ryoo IJ, Park HR, Choo SJ, Hwang JH, Park YM, Bae KH, Shin-ya K, Yoo ID (2006) Selective cytotoxic activity of Valinomycin against HT-29 human colon carcinoma cells via down-regulation of GRP78. Biol Pharm Bull 29:817–820

    Article  CAS  Google Scholar 

  20. Ogiso Y, Tomida A, Lei S, Omura S, Tsuruo T (2000) Proteasome inhibition circumvents solid tumor resistance to topoisomerase II-directed drugs. Cancer Res 60:2429–2434

    CAS  Google Scholar 

  21. Suzuki H, Tomida A, Tsuruo T (1998) A novel mutant from apoptosis-resistant colon cancer HT-29 cells showing hyper-apoptotic response to hypoxia, low glucose and cisplatin. Jpn J Cancer Res 89:1169–1178

    CAS  Google Scholar 

  22. Mancini M, Nicholson DW, Roy S, Thornberry NA, Peterson EP, Casciola-Rosen LA, Rosen A (1998) The caspase-3 precursor has a cytosolic and mitochondrial distribution: implications for apoptotic signaling. J Cell Biol 140:1485–1495

    Article  CAS  Google Scholar 

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Acknowledgements

This work is supported by the Kyungnam University Research Fund, 2007.

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Correspondence to Hae-Ryong Park.

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Jo, KJ., Cha, MR., Lee, MR. et al. Methanolic Extracts of Uncaria rhynchophylla Induce Cytotoxicity and Apoptosis in HT-29 Human Colon Carcinoma Cells. Plant Foods Hum Nutr 63, 77–82 (2008). https://doi.org/10.1007/s11130-008-0074-z

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