Synthetic hispidin, a PKC inhibitor, is more cytotoxic toward cancer cells than normal cells in vitro.

Abstract

The trypanocidal activity of naturally occurring 6-(3,4-dihydroxystyryl)-4-hydroxy-2-pyrone (hispidin) prompted us to examine its cytotoxic activity toward normal and cancerous cells in culture. Hispidin synthesized in our laboratory to a high degree of purity (checked by 1H and 13C NMR spectroscopy) was shown to be cytotoxic (between 10(-3) mol/L and 10(-7) mol/L) toward normal human MRC-5 fibroblasts, human cancerous keratinocytes (SCL-1 cell line), and human cancerous pancreatic duct cells (Capan-1 cell line). Interestingly, addition of hispidin in three successive doses (between 10(-5) mol/L and 10(-7) mol/L) led to a 100-fold increase in activity with an enhanced activity on cancer cells compared to normal cells (50%). Synthetic hispidin was found to inhibit isoform beta of protein kinase C (IC50 of 2 x 10(-6) mol/L), but not E. coli and placental type XV alkaline phosphatases. The enhanced activity of hispidin toward the cancerous cell lines is discussed.

• Authors: C Gonindard, C Bergonzi, C Denier, C Sergheraert, A Klaebe, L Chavant, E Hollande
• Journal: Cell biology and toxicology (Cell Biol Toxicol) Vol. 13 Issue 3 Pg. 141-53 (Mar 1997) ISSN: 0742-2091 [Print] Netherlands
• PMID: 9088624 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Growth Inhibitors
• Pyrones
• Protein Kinase C
• Alkaline Phosphatase
• hispidin

Topics

• Adenocarcinoma (drug therapy, pathology)
• Adult
• Alkaline Phosphatase (antagonists & inhibitors)
• Antineoplastic Agents (pharmacology)
• Basidiomycota (chemistry)
• Carcinoma, Squamous Cell (drug therapy, pathology)
• Cell Line
• Drug Screening Assays, Antitumor
• Facial Neoplasms (drug therapy, pathology)
• Fibroblasts (drug effects)
• Growth Inhibitors (pharmacology)
• Humans
• Keratinocytes (drug effects)
• Lung (cytology)
• Male
• Pancreatic Neoplasms (drug therapy, pathology)
• Protein Kinase C (antagonists & inhibitors)
• Pyrones (chemical synthesis, isolation & purification, pharmacology)
• Tumor Cells, Cultured