HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Synergistic interaction of selected marine animal anticancer drugs against human diffuse large cell lymphoma.

Abstract
We studied the antitumor effects of dolastatin 10, its structural modification, auristatin PE (TZT-1027), and vincristine alone and in combination with bryostatin 1 on a human diffuse large cell lymphoma line (WSU-DLCL2) in vitro and in vivo. WSU-DLCL2 cells were cultured in RPMI 1640 at a concentration of 2 x 10(5)/ml using a 24-well plate. Agents were added to triplicate wells, and cell count, viability, mitosis and apoptosis were assessed. Dolastatin 10 showed no apparent inhibition of cell growth at concentrations less than 500 pg/ ml. Auristatin PE showed significant growth inhibition at concentrations as low as 10 pg/ml, while vincristine had a minimal effect at 50 pg/ml. Dolastatin 10, auristatin PE and vincristine-treated cultures, at 50 pg/ml, exhibited 11, 1.7; 45, 11.8%; and 39, 25% mitosis and apoptosis, respectively. In the WSU-DLCL2 SCID mouse xenograft model, the efficacy of these agents alone or in combination with bryostatin 1 was evaluated. Tumor growth inhibition (T/C), tumor growth delay (T-C) and log10 kill for dolastatin 10, auristatin PE, vincristine and bryostatin 1 were 30%, 14 days and 1.4; 0.0%, 55 days and 5.5; 29.6%, 16 days and 1.6; and 39%, 7 days and 0.7, respectively. When given in combination, two out of five mice treated with auristatin PE + bryostatin 1 were free of tumors for 150 days and were considered cured. Dolastatin 10 + bryostatin 1 and vincristine + bryostatin 1 combinations were highly active but no cure was observed. We conclude that: (i) auristatin PE is more effective in this model than dolastatin 10, vincristine or bryostatin 1, (ii) auristatin PE can be administered at a concentration 10 times greater than dolastatin 10, and (iii) there is a synergistic effect between these agents and bryostatin 1, which is more apparent in the bryostatin 1 + auristatin PE combination. The use of these agents should be further explored clinically in the treatment of lymphoma.
AuthorsR M Mohammad, G R Pettit, V P Almatchy, N Wall, M Varterasian, A Al-Katib
JournalAnti-cancer drugs (Anticancer Drugs) Vol. 9 Issue 2 Pg. 149-56 (Feb 1998) ISSN: 0959-4973 [Print] England
PMID9510501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Bryostatins
  • Depsipeptides
  • Lactones
  • Macrolides
  • Oligopeptides
  • bryostatin 1
  • Vincristine
  • soblidotin
  • dolastatin 10
Topics
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Bryostatins
  • Depsipeptides
  • Drug Synergism
  • Humans
  • Lactones (administration & dosage)
  • Lymphoma, Large B-Cell, Diffuse (drug therapy)
  • Macrolides
  • Mice
  • Mice, Inbred ICR
  • Oligopeptides (administration & dosage, therapeutic use)
  • Time Factors
  • Tumor Cells, Cultured
  • Vincristine (administration & dosage)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: