Signature of mitochondria of steroidal hormones-dependent normal and cancer cells: potential molecular targets for cancer therapy

Front Biosci. 2007 Jan 1;12:154-73. doi: 10.2741/2056.

Abstract

The cross-talk between the cell nucleus and mitochondria appears to control hormone-induced signaling involved in the apoptosis, proliferation, and differentiation of both normal and malignant cells. Evaluation of the defects in genetics and physiology of human endocrine diseases, such as cancer, may manifest as a result of mitochondrial physiologic and metabolic compensation of genetic defects. Steroidal agents control biogenesis and maintenance of mitochondria through the crosstalk between nuclear and mitochondrial genomes. The regulation of mitochondrial transcription by steroidal hormones, presumably occurring through pathways similar to those that take place in the nucleus, opens a new way to better understand steroid hormone and vitamin action at the cellular level. In addition to the steroid hormone receptors, estrogen generated mitochondrial oxidants together with an estrogen-driven increase in epithelial cell proliferation have been shown to participate in the initiation and promotion of the neoplastic lesions in estrogen-sensitive tissues. Mitochondria generation of ROS appears to transduce signals to the nucleus for the activation of transcription factors involved in the cell cycle progression of estrogen-dependent cancer cells. Therefore, an in-depth analysis of such redox regulatory mechanisms is pertinent to the development of novel drugs and gene therapy strategies for the treatment of steroid hormone-dependent diseases related to mitochondrial disorders including cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Estrogen Receptor Modulators / pharmacology
  • Estrogens / pharmacology*
  • Glucocorticoids / pharmacology
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / genetics
  • Mitochondria / metabolism
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / therapy*
  • Vitamin D / pharmacology

Substances

  • Estrogen Receptor Modulators
  • Estrogens
  • Glucocorticoids
  • Vitamin D