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 105/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 RE 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 RE 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 RE combination. The use of these agents should be further explored clinically in the treatment of lymphoma.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 149-156 |
| Number of pages | 8 |
| Journal | Anti-Cancer Drugs |
| Volume | 9 |
| Issue number | 2 |
| State | Published - 1998 |
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Keywords
- Auristatin PE
- B cell
- Bryostatin 1
- Dolastatin 10
- SCID mice
- Vincristine
- Xenografts
ASJC Scopus subject areas
- Pharmacology
- Cancer Research
- Oncology
Cite this
Synergistic interaction of selected marine animal anticancer drugs against human diffuse large cell lymphoma. / Mohammad, Ramzi M.; Pettit, George; Almatchy, Victor P.; Wall, Nathan; Varterasian, Mary; Al-Katib, Ayad.
In: Anti-Cancer Drugs, Vol. 9, No. 2, 1998, p. 149-156.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synergistic interaction of selected marine animal anticancer drugs against human diffuse large cell lymphoma
AU - Mohammad, Ramzi M.
AU - Pettit, George
AU - Almatchy, Victor P.
AU - Wall, Nathan
AU - Varterasian, Mary
AU - Al-Katib, Ayad
PY - 1998
Y1 - 1998
N2 - 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 105/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 RE 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 RE 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 RE combination. The use of these agents should be further explored clinically in the treatment of lymphoma.
AB - 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 105/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 RE 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 RE 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 RE combination. The use of these agents should be further explored clinically in the treatment of lymphoma.
KW - Auristatin PE
KW - B cell
KW - Bryostatin 1
KW - Dolastatin 10
KW - SCID mice
KW - Vincristine
KW - Xenografts
UR - http://www.scopus.com/inward/record.url?scp=0031888974&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031888974&partnerID=8YFLogxK
M3 - Article
C2 - 9510501
AN - SCOPUS:0031888974
VL - 9
SP - 149
EP - 156
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
SN - 0959-4973
IS - 2
ER -