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

Ramzi M. Mohammad, George Pettit, Victor P. Almatchy, Nathan Wall, Mary Varterasian, Ayad Al-Katib

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalAnti-Cancer Drugs
Volume9
Issue number2
StatePublished - 1998

Fingerprint

dolastatin 10
Lymphoma, Large B-Cell, Diffuse
Vincristine
Pharmaceutical Preparations
Growth
Mitosis
Apoptosis
bryostatin 1
Neoplasms
SCID Mice
Heterografts
soblidotin
Cultured Cells
Lymphoma
Cell Survival

Keywords

  • Auristatin PE
  • B cell
  • Bryostatin 1
  • Dolastatin 10
  • SCID mice
  • Vincristine
  • Xenografts

ASJC Scopus subject areas

  • Pharmacology
  • Cancer Research
  • Oncology

Cite this

Mohammad, R. M., Pettit, G., Almatchy, V. P., Wall, N., Varterasian, M., & Al-Katib, A. (1998). Synergistic interaction of selected marine animal anticancer drugs against human diffuse large cell lymphoma. Anti-Cancer Drugs, 9(2), 149-156.

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 journalArticle

Mohammad, RM, Pettit, G, Almatchy, VP, Wall, N, Varterasian, M & Al-Katib, A 1998, 'Synergistic interaction of selected marine animal anticancer drugs against human diffuse large cell lymphoma', Anti-Cancer Drugs, vol. 9, no. 2, pp. 149-156.
Mohammad, Ramzi M. ; Pettit, George ; Almatchy, Victor P. ; Wall, Nathan ; Varterasian, Mary ; Al-Katib, Ayad. / Synergistic interaction of selected marine animal anticancer drugs against human diffuse large cell lymphoma. In: Anti-Cancer Drugs. 1998 ; Vol. 9, No. 2. pp. 149-156.
@article{a4bb165ff6d74b519eebe520cb9cf3c4,
title = "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 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.",
keywords = "Auristatin PE, B cell, Bryostatin 1, Dolastatin 10, SCID mice, Vincristine, Xenografts",
author = "Mohammad, {Ramzi M.} and George Pettit and Almatchy, {Victor P.} and Nathan Wall and Mary Varterasian and Ayad Al-Katib",
year = "1998",
language = "English (US)",
volume = "9",
pages = "149--156",
journal = "Anti-Cancer Drugs",
issn = "0959-4973",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

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 -