Synthetic hispidin, a PKC inhibitor, is more cytotoxic toward cancer cells than normal cells in vitro.
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.
Gonindard
C
C
Laboratoire de biologie Cellulaire, Université Paul Sabatier, Toulouse, France.
Bergonzi
C
C
Denier
C
C
Sergheraert
C
C
Klaebe
A
A
Chavant
L
L
Hollande
E
E
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001487:Basidiomycota / Q000737:chemistry; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D002460:Cell Line; D004354:Drug Screening Assays, Antitumor; D005153:Facial Neoplasms / Q000188:drug therapy / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D008168:Lung / Q000166:cytology; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011753:Pyrones / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D011753:Pyrones; D011493:Protein Kinase C; D000469:Alkaline Phosphatase; C007946:hispidin