Retinoic acid and calcitriol inhibition of growth and NADH oxidase of normal and immortalized human keratinocytes

Biochim Biophys Acta. 1992 Apr 7;1134(3):217-22. doi: 10.1016/0167-4889(92)90179-f.


Plasma membranes were isolated by aqueous two-phase partition from normal human keratinocytes (HKc) and from human keratinocytes immortalized with human papillomavirus type 16 DNA (HKc/HPV16). The NADH oxidase of plasma membrane vesicles of normal HKc was stimulated by epidermal growth factor whereas that of HKc/HPV16 was not. The NADH oxidase of the plasma membranes from both normal HKc and HKc/HPV16 was inhibited by calcitriol (1 alpha-1,25-dihydroxy vitamin D-3) and retinoic acid. However, with plasma membranes from HKc/HPV16 the NADH oxidase was more susceptible to inhibition by retinoic acid than were membranes from normal HKc. Similarly, clonal growth of HKc/HPV16 was inhibited by retinoic acid at lower concentrations than normal HKc whereas inhibition of clonal growth of normal HKc and HKc/HPV16 by calcitriol showed similar dose-dependencies. Comparing normal HKc and HKc/HPV16, the results demonstrate parallel inhibition of clonal growth and NADH oxidase by both retinoic acid and calcitriol of HKc/HPV16 but not of normal HKc. These results suggest that an increased sensitivity of the plasma membrane NADH oxidase of HKc/HPV16 to retinoic acid may be related to the increased sensitivity of these cells to growth control by retinoic acid. In addition, since plasma membrane NADH oxidase of HKc/HPV16 shows altered responsiveness to growth modulators such as EGF, retinoic acid and calcitriol, it appears that HKc/HPV16 express an NADH oxidase with different characteristics than those of normal HKc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcitriol / pharmacology*
  • Cell Division / drug effects*
  • Cell Line, Transformed
  • Cell Membrane / drug effects
  • Cells, Cultured
  • Colony-Forming Units Assay
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / drug effects*
  • Keratinocytes / enzymology
  • Multienzyme Complexes / antagonists & inhibitors*
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors*
  • Tretinoin / pharmacology*


  • Multienzyme Complexes
  • Tretinoin
  • NADH oxidase
  • NADH, NADPH Oxidoreductases
  • Calcitriol