Carnosol delays chemotherapy-induced DNA fragmentation and morphological changes associated with apoptosis in leukemic cells

Susan J. Zunino, David H. Storms

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Carnosol, from the herb rosemary, has been shown to induce apoptotic cell death in high-risk pre-B acute lymphoblastic leukemia (ALL). In the present study, carnosol was tested for its ability to sensitize leukemia cells to chemotherapeutic agents. Carnosol reduced the percentage of cell death in the pre-B ALL lines SEM, RS4;11, and REH when combined with cytarabine, methotrexate, or vincristine compared to the chemotherapeutic agents alone. Analysis of DNA strand breaks by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that carnosol delayed DNA cleavage in the cells when combined with chemotherapeutic drugs. Co-treatment of the cells with carnosol and chemotherapeutic drugs did not reduce mitochondrial membrane depolarization compared to the drug treatment alone. Time course analysis of caspase-3 activation by flow cytometry showed co-treatment with carnosol and drugs increased the activation of caspase-3 above that observed for the chemotherapeutic drugs alone. A lower percentage of caspase-3 positive cells progressed to an apoptotic phenotype when co-treated with carnosol and the chemotherapeutic drugs compared to drugs alone. These data show that carnosol blocks the terminal apoptotic events induced by chemotherapeutic drugs and suggest that increased dietary intake of carnosol may potentially decrease the effectiveness of some standard chemotherapy treatments used for leukemia.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalNutrition and Cancer
Volume61
Issue number1
DOIs
StatePublished - Jan 2009

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DNA Fragmentation
Apoptosis
Drug Therapy
Pharmaceutical Preparations
Caspase 3
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Cell Death
carnosol
DNA Cleavage
DNA Breaks
DNA Nucleotidylexotransferase
Cytarabine
Mitochondrial Membranes
Vincristine
Therapeutics
Methotrexate
Flow Cytometry
Phenotype

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Oncology
  • Cancer Research

Cite this

Carnosol delays chemotherapy-induced DNA fragmentation and morphological changes associated with apoptosis in leukemic cells. / Zunino, Susan J.; Storms, David H.

In: Nutrition and Cancer, Vol. 61, No. 1, 01.2009, p. 94-102.

Research output: Contribution to journalArticle

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