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A possible mechanism for the cytotoxicity of a polyacetylenic alcohol, panaxytriol: inhibition of mitochondrial respiration


A polyacetylenic alcohol, panaxytriol, isolated fromPanax ginseng C. A. Meyer inhibits both tumor cell growth into mice. Our preliminary studies indicated that panaxytriol localizes to the mitochondria in human breast carcinoma cells (Breast M25-SF). This study focused on the effects of panaxytriol on mitochondrial structures and function in Breast M25-SF. The results indicate that panaxytriol rapidly inhibits cellular respiration and disrupts cellular energy balance in Breast M25-SF. At concentrations between 11.3 and 180 μM, panaxytriol causes a dose-dependent inhibition of the conversion of the tetrazolium (MTT assay) by mitochondrial dehydrogenase within 2 h. A 1-h treatment with 180 μM panaxytriol causes a significant loss of rhodamine-123 from cells with mitochondria prestained with rhodamine-123 (by flow cytometry). Specific toxic changes were observed by electron microscopy in the mitochondria of Breast M25-SF within 1 h after treatment with more than 180 μM panaxytriol. These data indicate that 180 μM panaxytriol rapidly disrupts cellular energy balance and respiration in Breast M25-SF and suggest that panaxytriol may lower cellular ATP concentrations. After treatment with 180 μM panaxytriol, cellular ATP levels were 40% of those in control cells after 1 h. ATP depletion preceded the loss of cellular viability. Neither ATP depletion nor cytolysis was found in human erythrocytes that have no mitochondria. Thus, ATP depletion resulting from a direct inhibition of mitochondrial respiration is a critical early in the cytotoxicity of panaxytriol.

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  1. 1.

    Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1989) Biosynthesis and the creation of order. In: Racker E (ed) Molecular biology of the cell, 2nd edn., Garland, New York, p 73

  2. 2.

    Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD (1989) Energy conversion: mitochondria and chloroplasts. In: Brand M (ed) Molecular biology of the cell, 2nd edn., Garland, New York, p 355

  3. 3.

    Andrews PA, Albright KD (1992) Mitochondrial defects incis-diamminedichloroplatinum(II)-resistant human ovarian carcinoma cells. Cancer Res 52:1895

  4. 4.

    Cannon JR, Harvison PJ, Rush GF (1991) The effects of fructose on adenosine triphosphate depletion following mitochondrial dysfunction and lethal cell injury in isolated rat hepatocytes. Toxicol Appl Pharmacol 108:407

  5. 5.

    Durand R, Briand Y, Touraille S, Alziari S (1981) Molecular approaches to phosphate transport in mitochondria. Trends Biochem Sci 6:211

  6. 6.

    Graham JK, Kunze E, Hammerstedt RH (1990) Analysis of sperm cell viability, acrosomal intergrity, and mitochondrial function using flow cytometry. Biol Reprod 43:55

  7. 7.

    Hogeboom GH (1955) Fractionation of cell components of animal tissues. Methods in enzymology, vol. 1. Academic Press, New York, p 16

  8. 8.

    Houghton PJ, Bailey FC, Houghton JA, Murti KG, Howbert JJ, Grindey GB (1990) Evidence for mitochondrial localization ofN-(4-methylphenylsulfonyl)-N′-(4-chlorophenyl)urea in human colon adenocarcinoma cells. Cancer Res 50:664

  9. 9.

    Johnson LV, Walsh ML, Chen LB (1980) Localization of mitochondria in living cells with rhodamine-123. Proc Natl Acad Sci USA 77:990

  10. 10.

    Johnson LV, Walsh ML, Bockus BJ, Chen LB (1981) Monitoring of relative mitochondrial membrane in living cells by fluorescence microscopy. J Cell Biology 88:526

  11. 11.

    Katano M, Matsunaga H, Yamamoto H (1988) A tumor inhibitory substance fromPanax ginseng (in Japanese). J Jpn Surg Soc 89:971

  12. 12.

    Katano M, Yamamoto H, Matsunaga H, Mori M, Takata K, Nakamura M (1990) Cell growth inhibitory substance isolated fromPanax ginseng root: panaxytriol. (in Japanese with English summary) Jpn J Cancer Chemother 17:1045

  13. 13.

    Keler T, Smith CAD (1989) Effects on growth and energy metabolism in untransformed and transformed BALB/c mouse fibroblasts by a novel cytotoxic compound. Cancer Res 49:7093

  14. 14.

    Klingenberg M (1979) The ADP, ATP shuttle of the mitochondrion. Trends Biochem Sci 4:249

  15. 15.

    Lee KD, Huemer RP (1971) Antitumoral activity ofPanax ginseng extracts. Jpn J Pharmacol 21:299

  16. 16.

    Lucchesi BR, Mullane KM (1986) Leukocytes and ischemiainduced myocardial injury. Annu Rev Pharmacol Toxicol 26:201

  17. 17.

    Matsunaga H, Katano M, Yamamoto H, Mori M, Takata K (1989) Studies on the panaxytriol ofPanax ginseng C. A. Meyer. Isolation, determination and antitumor activity. Chem Pharm Bull 37:1279

  18. 18.

    Matsunaga H, Katano M, Yamamoto H, Fujito H, Mori M, Takata K (1990) Cytotoxic activity of polyacetylene compounds inPanax ginseng C. A. Meyer. Chem Pharm Bull 38:3480

  19. 19.

    Matsunaga H, Katano M, Saita T, Yamamoto H, Mori M (1994) Potentiation of cytotoxicity of mitomycin C by a polyacetylenic alcohol, panaxytriol. Cancer Chemother Pharmacol 33:291

  20. 20.

    Modica-Napolitano JS, Joyal JL, Ara G, Aprille JR (1990) Mitochondrial toxicity of cationic photosensitizers for photochemotherapy. Cancer Res 50:7876

  21. 21.

    Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55

  22. 22.

    Rago R, Mitchen J, Cheng AL, Oberley T, Wilding G (1991) Disruption of cellular energy balance by suramin in intact human prostatic carcinoma cells, a likely antiproliferative mechanism. Cancer Res 51:6629

  23. 23.

    Saita T, Matsunaga H, Yamamoto H, Nagumo F, Fujito H, Mori M, Katano M (1994) A highly sensitive enzyme-linked immunosorbent assay (ELISA) for antitumor polyacetylenic alcohol, panaxytriol. Biol Pharm Bull 17:798

  24. 24.

    Shapiro HM, Natale PJ, Kamentsky LA (1979) Estimation of membrane potentials of individual lymphocytes by flow cytometry. Proc Natl Acad Sci USA 76:5728

  25. 25.

    Slater TF, Sawyer B, Sträuli U (1963) Studies on succinatetetrazolium reductase systems. III. Points of coupling of four different tetrazolium salts. Biochim Biophys Acta 77:383

  26. 26.

    Thakar JH, Chapin C, Berg RH, Ashmun RA, Houghton PJ (1991) Effect of antitumor diarylsulfonylureas on in vivo and in vitro mitochondrial structure and functions. Cancer Res 51:6286

  27. 27.

    Ueda T, Ishida Y (1987) High-performance liquid chromatographic separation of biological macromolecules on new silica-based ion exchangers. J Chromatogr 386:273

  28. 28.

    Vernetti LA, MacDonald JR, Wolfgang GHI, Dominick MA, Pegg DG (1993) ATP depletion is associated with cytotoxicity of a novel lipid regulator in guinea pig adrenocortical cells. Toxicol Appl Pharmacol 118:30

  29. 29.

    Wu EY, Smith MT, Bellomo G, Di Monte D (1990) Relationships between the mitochondrial transmembrane potential, ATP concentration, and cytotoxicity in isolated rat hepatocytes. Arch Biochem Biophys 282:358

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Correspondence to M. Katano.

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Matsunaga, H., Saita, T., Nagumo, F. et al. A possible mechanism for the cytotoxicity of a polyacetylenic alcohol, panaxytriol: inhibition of mitochondrial respiration. Cancer Chemother. Pharmacol. 35, 291–296 (1995). https://doi.org/10.1007/BF00689447

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Key words

  • Polyacetylenic alcohol
  • Panaxytriol
  • Mitochondrial respiration
  • MTT assay
  • Rhodamine-123 ATP level