The chemopreventive agent myoinositol inhibits Akt and extracellular signal-regulated kinase in bronchial lesions from heavy smokers

Cancer Prev Res (Phila). 2009 Apr;2(4):370-6. doi: 10.1158/1940-6207.CAPR-08-0209. Epub 2009 Mar 31.


Myoinositol is an isomer of glucose that has chemopreventive activity in animal models of cancer. In a recent phase I clinical trial, myoinositol administration correlated with a statistically significant regression of preexisting bronchial dysplastic lesions in heavy smokers. To shed light on the potential mechanisms involved, activation of Akt and extracellular signal-regulated kinase (ERK), two kinases that control cellular proliferation and survival, was assessed in 206 paired bronchial biopsies from 21 patients who participated in this clinical trial. Before myoinositol treatment, strongly positive staining for activation of Akt was detected in 27% of hyperplastic/metaplastic lesions and 58% of dysplastic lesions (P = 0.05, chi(2) test). There was also a trend toward increased activation of ERK (28% in regions of hyperplasia/metaplasia to 42% of dysplastic lesions). Following myoinositol treatment, significant decreases in Akt and ERK phosphorylation were observed in dysplastic (P < 0.01 and 0.05, respectively) but not hyperplastic/metaplastic lesions (P > 0.05). In vitro, myoinositol decreased endogenous and tobacco carcinogen-induced activation of Akt and ERK in immortalized human bronchial epithelial cells, which decreased cell proliferation and induced a G(1)-S cell cycle arrest. These results show that the phenotypic progression of premalignant bronchial lesions from smokers correlates with increased activation of Akt and ERK and that these kinases are targets of myoinositol. Moreover, they suggest that myoinositol might cause regression of bronchial dysplastic lesions through inhibition of active Akt and ERK.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Bronchial Diseases / drug therapy*
  • Bronchial Diseases / enzymology
  • Bronchial Diseases / etiology
  • Cell Line
  • Cell Proliferation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / biosynthesis
  • Extracellular Signal-Regulated MAP Kinases / drug effects*
  • Female
  • Humans
  • Immunohistochemistry
  • Inositol / therapeutic use*
  • Lung Neoplasms / prevention & control
  • Male
  • Middle Aged
  • Phosphorylation
  • Precancerous Conditions / drug therapy
  • Precancerous Conditions / enzymology
  • Proto-Oncogene Proteins c-akt / biosynthesis
  • Proto-Oncogene Proteins c-akt / drug effects*
  • Smoking / adverse effects*


  • Antineoplastic Agents
  • Inositol
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases