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Apoptosis induction by the natural product cancer chemopreventive agent deguelin is mediated through the inhibition of mitochondrial bioenergetics

Apoptosis volume 9, pages 437–447 (2004)Cite this article

Abstract

Deguelin exhibits chemopreventive properties in animal carcinogenesis models. The mechanism underpinning the chemopreventive effects of deguelin has not been fully elucidated. However, it has been suggested that this agent reduces ornithine decarboxylase activity, and perhaps the activity of other signaling intermediates associated with tumorigenesis, by inhibiting mitochondrial bioenergetics. We sought to determine if deguelin could trigger apoptosis by inhibiting mitochondrial bioenergetics. Therefore, we compared and contrasted the effects of deguelin on cells from two human cutaneous squamous cell carcinoma cell lines (parental cells) and their respiration-deficient clones lacking mitochondrial DNA (ρ0). While deguelin promoted marked apoptosis in the parental cells in a dose- and time-dependent manner, it failed to do so in the ρ0 clones. Furthermore, short-term exposure to deguelin diminished oxygen consumption by the parental cells and promoted mitochondrial permeability transition as evidenced by the dissipation of mitochondrial inner transmembrane potential, reactive oxygen species production, cardiolipin peroxidation, caspase activation, and mitochondrial swelling. Mitochondrial permeability transition was not observed in the ρ0 clones exposed to deguelin. These results demonstrate that deguelin induces apoptosis in skin cancer cells by inhibiting mitochondrial bioenergetics and provide a novel mechanism for the putative anticancer activity of this agent.

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  1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA

    N. Hail Jr. & R. Lotan

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  1. N. Hail Jr.
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  2. R. Lotan
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Correspondence to N. Hail Jr..

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Hail, N., Lotan, R. Apoptosis induction by the natural product cancer chemopreventive agent deguelin is mediated through the inhibition of mitochondrial bioenergetics. Apoptosis 9, 437–447 (2004). https://doi.org/10.1023/B:APPT.0000031449.57551.e1

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  • Issue Date:

  • DOI: https://doi.org/10.1023/B:APPT.0000031449.57551.e1

  • apoptosis
  • cancer chemoprevention
  • deguelin
  • mitochondria
  • mitochondrial bioenergetics
  • mitochondrial permeability transition