Antitumor activity of enzastaurin (LY317615.HCl) against human cancer cell lines and freshly explanted tumors investigated in in-vitro [corrected] soft-agar cloning experiments

Invest New Drugs. 2007 Jun;25(3):205-10. doi: 10.1007/s10637-007-9038-7. Epub 2007 Mar 9.


Enzastaurin (LY317615.HCl) is an antiproliferative agent targeted specifically against PKC-beta. We have investigated the antitumoral effects of Enzastaurin against human cancer cell lines and freshly explanted human tumor tissue. Ten human cancer cell lines (NSCLC, colon, and thyroid) and human tumor specimens from 72 patients were used for in vitro studies in a cloning assay (HTCA). Cell lines and primary tumor cells were exposed to Enzastaurin for either 1 h or 7 days, or for 1 h or 21 days. At clinically achievable concentrations of Enzastaurin, inhibition of cell growth was observed for lung, colorectal, and thyroid cancer cell lines in a concentration dependent manner. Patient specimens exposed 1 h or 21 days to 1,400 nM Enzastaurin demonstrated inhibition rates of 24 and 32%, respectively. Marked inhibitory effects were observed in breast, thyroid, head/neck, non-small cell lung cancer, pancreatic cancer, and melanoma. In addition to its established antiangiogenic effects, Enzastaurin has direct antitumor activity against established human cancer cell lines and primary tumor specimens. This warrants further clinical development in tumors which have been identified to be potentially sensitive to Enzastaurin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agar
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Culture Media
  • Dose-Response Relationship, Drug
  • Humans
  • Indoles / pharmacology*
  • Neoplasms / enzymology
  • Neoplasms / pathology*
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / enzymology
  • Neoplastic Stem Cells / pathology
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase C / metabolism
  • Protein Kinase C beta
  • Protein Kinase Inhibitors / pharmacology*
  • Time Factors
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay


  • Antineoplastic Agents
  • Culture Media
  • Indoles
  • Protein Kinase Inhibitors
  • Agar
  • Protein Kinase C
  • Protein Kinase C beta
  • enzastaurin