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

Publication ,  Journal Article
Han, W; Gills, JJ; Memmott, RM; Lam, S; Dennis, PA
Published in: Cancer Prev Res (Phila)
April 2009

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.

Duke Scholars

Published In

Cancer Prev Res (Phila)

DOI

EISSN

1940-6215

Publication Date

April 2009

Volume

2

Issue

4

Start / End Page

370 / 376

Location

United States

Related Subject Headings

  • Smoking
  • Proto-Oncogene Proteins c-akt
  • Precancerous Conditions
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Inositol
  • Immunohistochemistry
 

Citation

APA
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MLA
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Han, W., Gills, J. J., Memmott, R. M., Lam, S., & Dennis, P. A. (2009). The chemopreventive agent myoinositol inhibits Akt and extracellular signal-regulated kinase in bronchial lesions from heavy smokers. Cancer Prev Res (Phila), 2(4), 370–376. https://doi.org/10.1158/1940-6207.CAPR-08-0209
Han, Wei, Joell J. Gills, Regan M. Memmott, Stephen Lam, and Phillip A. Dennis. “The chemopreventive agent myoinositol inhibits Akt and extracellular signal-regulated kinase in bronchial lesions from heavy smokers.Cancer Prev Res (Phila) 2, no. 4 (April 2009): 370–76. https://doi.org/10.1158/1940-6207.CAPR-08-0209.
Han W, Gills JJ, Memmott RM, Lam S, Dennis PA. 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.
Han, Wei, et al. “The chemopreventive agent myoinositol inhibits Akt and extracellular signal-regulated kinase in bronchial lesions from heavy smokers.Cancer Prev Res (Phila), vol. 2, no. 4, Apr. 2009, pp. 370–76. Pubmed, doi:10.1158/1940-6207.CAPR-08-0209.
Han W, Gills JJ, Memmott RM, Lam S, Dennis PA. 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):370–376.

Published In

Cancer Prev Res (Phila)

DOI

EISSN

1940-6215

Publication Date

April 2009

Volume

2

Issue

4

Start / End Page

370 / 376

Location

United States

Related Subject Headings

  • Smoking
  • Proto-Oncogene Proteins c-akt
  • Precancerous Conditions
  • Phosphorylation
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Lung Neoplasms
  • Inositol
  • Immunohistochemistry