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

Abstract

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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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