Skip to main content
Log in

Anticancer activity of 28-Oxoallobetulin on HT-29 human colon cancer cells

  • Research Article
  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

Many successful therapeutic drug, including several anticancer agents, have been isolated for natural products. In a recent screen of methanolic extracts from several natural products, we isolated an active compound, from the methanolic extract of persimmon calyx, which promoted cytotoxicity and apoptosis in HT-29 human colon cancer cells. This compound was identified as 28-oxoallobetulin, a prototypical compound, by UV-MS analysis and various NMR spectroscopic methods. The highly cytotoxic effects of 28-oxoallobetulin on HT-29 cells were demonstrated using MTT reduction, LDH release, and colony formation assays. Furthermore, we were able to detect apoptotic bodies in HT-29 cells by Hoechst staining as well as flow cytometric analysis for the presence of sub-G1 DNA peaks, indicative of apoptotic cells. Finally apoptosis in HT-29 cells following 28-oxoallobetulin treatment was also confirmed by the presence of activated caspase-3 and specific proteolytic cleavage of poly (ADP-ribose) polymerase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Doll R, Reto R. The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst. 66: 1191–1308 (1981)

    CAS  Google Scholar 

  2. Rho SN, Han JH. Cytotoxicity of garlic and onion methanol extract on human lung cancer cell lines. J. Korean Soc. Food Sci. Nutr. 29: 870–874 (2000)

    Google Scholar 

  3. Goodman GE, Yen YP, Cox TC, Crowley J. Effect of verapamil on in vitro cytotoxicity of adriamycin and vinblastine in human tumor cells. Cancer Res. 47: 2295–2304 (1987)

    CAS  Google Scholar 

  4. Cuffy M, Abir F, Longo WE. Management of less common tumors of the colon, rectum, and anus. Clin. Colorectal Cancer 5: 327–337 (2006)

    Article  Google Scholar 

  5. Brown JM, Giaccia AJ. The unique physiology of solid tumor: Opportunities (and problems) for cancer therapy. Cancer Res. 58: 1408–1416 (1998)

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Jo KY, Cha MR, Lee MR, Yoon MY, Park HR. Methanolic extracts of Uncaria rhynchophylla induce cytotoxicity and apoptosis in HT-29 human colon carcinoma cells. Plant Food. Hum. Nutr. 63: 77–82 (2008)

    Article  Google Scholar 

  8. McBurney MI, Van Soest PJ, Jeraci JL. Colonic carcinogenesis: The microbial feast or famine mechanism. Nutr. Cancer 10: 23–28 (1987)

    Article  CAS  Google Scholar 

  9. Shaw P, Costa J. Molecular biology of colon cancer (review). Anticancer Res. 9: 21–27 (1989)

    CAS  Google Scholar 

  10. Aharinejad S, Sioud M, Lucas T, Abraham D. Target validation using RNA interference in solid tumors. Methods Mol. Biol. 361: 227–238 (2007)

    CAS  Google Scholar 

  11. Kim JY, Hwang JH, Cha MR, Yoon MY, Son ES, Tomida A, Ko B, Song SW, Shin-Ya K, Hwang YI, Park HR. Arctigenin blocks the unfolded protein response and shows therapeutic antitumor activity. J. Cell Physiol. 224: 33–40 (2010)

    CAS  Google Scholar 

  12. Panchal RG. Novel therapeutic strategies to selectively kill cancer cells. Biochem. Pharmacol. 55: 247–252 (1998)

    Article  CAS  Google Scholar 

  13. Lee EO, Lee JR, Kim KH, Baek NI, Lee SJ, Lee BH, Cho KD, Ahn KS, Kim SH. The methylene chloride fraction of trichosanthis fructus induces apoptosis in U937 cells through the mitochondrial pathway. Biol. Pharm. Bull. 29: 21–25 (2006)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  15. Ischenko I, Seeliger H, Schaffer M, Jauch KW, Bruns CJ. Cancer stem cells: How can we target them. Curr. Med. Chem. 15: 3171–3184 (2008)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  17. 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 Inst. 96: 1300–1310 (2004)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  19. Park HR, Furihata K, Hayakawa Y, Shin-Ya K. Versipelostatin, a novel GRP78/BiP molecular chaperone down-regulator of microbial origin. Tetrahedron Lett. 43: 6941–6945 (2002)

    Article  CAS  Google Scholar 

  20. Ahn HS, Jeon TI, Lee JY, Hwang SG, Lim Y, Park DK. Antioxidative activity of persimmon and grape seed extract: In vitro and in vivo. Nutr. Res. 22: 1265–1273 (2002)

    Article  CAS  Google Scholar 

  21. Gorinstein S, Zemser M, Weisz M, Halevy S, Deutsch J, Tilus K, Feintuch D, Guerra N, Fishman M, Bartnikowska E. Fluorometric analysis of phenolics in persimmons. Biosci. Biotech Bioch. 58: 1087–1092 (1994)

    Article  CAS  Google Scholar 

  22. Thibeault D, Gauthier C, Legault J, Bouchard J, Dufour P, Pichette A. Synthesis and structure-activity relationship study of cytotoxic germanicane- and lupine-type 3beta-O-monodesmosidic saponins starting from betulin. Bloorg. Med. Chem. 15: 6144–6157 (2007)

    Article  CAS  Google Scholar 

  23. Gauthier C, Legault J, Piochon M, Lavoie S, Tremblay S, Pichette A. Synthesis, sytotoxicity, and haemolytic activity of chacotrioside lupine-type neosaponins and their germanicane-type rearrangement products. Bioorg. Med. Chem. Lett. 19: 2310–2314 (2009)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. Green DR, Reed JC. Mitochondria and apoptosis. Science 281: 1309–1312 (1998)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hae-Ryong Park.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, JM., Koo, D. & Park, HR. Anticancer activity of 28-Oxoallobetulin on HT-29 human colon cancer cells. Food Sci Biotechnol 23, 1321–1325 (2014). https://doi.org/10.1007/s10068-014-0181-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-014-0181-6

Keywords

Navigation