Inhibition of hepatic tumor cell proliferation in vitro and tumor growth in vivo by taltobulin, a synthetic analogue of the tripeptide hemiasterlin.
OBJECTIVE
To investigate the inhibitory effects of taltobulin (HTI-286), a synthetic analogue of natural hemiasterlin derived from marine sponges, on hepatic tumor growth in vitro and in vivo.


METHODS
The potential anti-proliferative effects of HTI-286 on different hepatic tumor cell lines in vitro and in vivo were examined.


RESULTS
HTI-286 significantly inhibited proliferation of all three hepatic tumor cell lines (mean IC50 = 2 nmol/L +/- 1 nmol/L) in vitro. Interestingly, no decrease in viable primary human hepatocytes (PHH) was detected under HTI-286 exposure. Moreover, intravenous administration of HTI-286 significantly inhibited tumor growth in vivo (rat allograft model).


CONCLUSIONS
HTI-286 might be considered a potent promising drug in treatment of liver malignancies. HTI-286 is currently undergoing clinical evaluation in cancer patients.
Vashist
Yogesh-K
YK
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Germany.
Tiffon
Celine
C
Stoupis
Christoforos
C
Redaelli
Claudio-A
CA
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008870:Microtubules / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D050257:Tubulin Modulators / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
C473896:HTI-286; D009842:Oligopeptides; D050257:Tubulin Modulators; C467070:hemiasterlin