Bryostatin 1 induces apoptosis and augments inhibitory effects of vincristine in human diffuse large cell lymphoma

Ramzi M. Mohammad, Hariharan Diwakaran, Auday Maki, Mohamed A. Emara, George Pettit, Bruce Redman, Ayad Al-Katib

Research output: Contribution to journalArticle

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Abstract

Bryostatin 1 (Bryo1), a macrocyclic lactone and a protein kinase C activator, is isolated from the marine bryozoan Bugula neritina. In this study we describe its effect, alone or after sequential use with vincristine (VCR), on the human diffuse large cell lymphoma cell line WSU-DLCL2. Our results show that both Bryo1 and VCR induced apoptosis as demonstrated by morphological examination, DNA flow cytometry (FCM), and DNA fragmentation on agarose gel electrophoresis. Cells pretreated for 24 h with Bryo1 and then exposed to VCR showed an increase in apoptosis compared to cells that were exposed to Bryo1 or VCR alone. We also studied the effects of Bryo1, VCR and their combination on cell growth, bcl-2 and p53 expression, and inhibition of cell proliferation as measured by [3H]-thymidine incorporation. Cell analysis showed significant growth inhibition of WSU-DLCL2 cells by the Bryo1/VCR combination as compared to either agent alone. Immunocytochemistry (ICC) revealed that relative bcl-2 oncoprotein expression was decreased in cells treated with Bryo1, or VCR separately and was abolished by combining both drugs. When examined by ICC, WSU-DLCL2 cells were initially negative for the p53 protein. However, upon treatment with the above agents, the relative expression of p53 was moderate on Bryo1-or VCR-treated cells and strong on cells treated with the Bryo1/VCR combination. Cell proliferation as measured by [3H]-thymidine incorporation revealed significant inhibition of tumor growth by exposure to the agents when compared to the control. In contrast, Bryo1, VCR and their combination did not show any inhibition of normal bone marrow growth. These findings taken together, suggest that the exposure of WSU-DLCL2 cells to Bryo1 prior to treatment with VCR enhances apoptosis, a phenomenon which might be exploited for future therapies.

Original languageEnglish (US)
Pages (from-to)667-673
Number of pages7
JournalLeukemia Research
Volume19
Issue number9
DOIs
StatePublished - 1995

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Vincristine
Apoptosis
Thymidine
bryostatin 1
Growth
Immunohistochemistry
Cell Proliferation
Agar Gel Electrophoresis
Oncogene Proteins
Bone Development
Lactones
DNA Fragmentation
Protein Kinase C
Flow Cytometry
Therapeutics
Bone Marrow

Keywords

  • apoptosis
  • B-cell
  • bcl-2
  • bryostatin 1
  • diffuse large cell lymphoma
  • immunocytochemistry
  • p53
  • vincristine
  • [H]-thymidine

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

Cite this

Bryostatin 1 induces apoptosis and augments inhibitory effects of vincristine in human diffuse large cell lymphoma. / Mohammad, Ramzi M.; Diwakaran, Hariharan; Maki, Auday; Emara, Mohamed A.; Pettit, George; Redman, Bruce; Al-Katib, Ayad.

In: Leukemia Research, Vol. 19, No. 9, 1995, p. 667-673.

Research output: Contribution to journalArticle

Mohammad, Ramzi M. ; Diwakaran, Hariharan ; Maki, Auday ; Emara, Mohamed A. ; Pettit, George ; Redman, Bruce ; Al-Katib, Ayad. / Bryostatin 1 induces apoptosis and augments inhibitory effects of vincristine in human diffuse large cell lymphoma. In: Leukemia Research. 1995 ; Vol. 19, No. 9. pp. 667-673.
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AB - Bryostatin 1 (Bryo1), a macrocyclic lactone and a protein kinase C activator, is isolated from the marine bryozoan Bugula neritina. In this study we describe its effect, alone or after sequential use with vincristine (VCR), on the human diffuse large cell lymphoma cell line WSU-DLCL2. Our results show that both Bryo1 and VCR induced apoptosis as demonstrated by morphological examination, DNA flow cytometry (FCM), and DNA fragmentation on agarose gel electrophoresis. Cells pretreated for 24 h with Bryo1 and then exposed to VCR showed an increase in apoptosis compared to cells that were exposed to Bryo1 or VCR alone. We also studied the effects of Bryo1, VCR and their combination on cell growth, bcl-2 and p53 expression, and inhibition of cell proliferation as measured by [3H]-thymidine incorporation. Cell analysis showed significant growth inhibition of WSU-DLCL2 cells by the Bryo1/VCR combination as compared to either agent alone. Immunocytochemistry (ICC) revealed that relative bcl-2 oncoprotein expression was decreased in cells treated with Bryo1, or VCR separately and was abolished by combining both drugs. When examined by ICC, WSU-DLCL2 cells were initially negative for the p53 protein. However, upon treatment with the above agents, the relative expression of p53 was moderate on Bryo1-or VCR-treated cells and strong on cells treated with the Bryo1/VCR combination. Cell proliferation as measured by [3H]-thymidine incorporation revealed significant inhibition of tumor growth by exposure to the agents when compared to the control. In contrast, Bryo1, VCR and their combination did not show any inhibition of normal bone marrow growth. These findings taken together, suggest that the exposure of WSU-DLCL2 cells to Bryo1 prior to treatment with VCR enhances apoptosis, a phenomenon which might be exploited for future therapies.

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