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 language | English (US) |
|---|---|
| Pages (from-to) | 94-102 |
| Number of pages | 9 |
| Journal | Nutrition and Cancer |
| Volume | 61 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2009 |
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ASJC Scopus subject areas
- Medicine (miscellaneous)
- Nutrition and Dietetics
- Oncology
- Cancer Research
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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 journal › Article
}
TY - JOUR
T1 - Carnosol delays chemotherapy-induced DNA fragmentation and morphological changes associated with apoptosis in leukemic cells
AU - Zunino, Susan J.
AU - Storms, David H.
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=58149173326&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58149173326&partnerID=8YFLogxK
U2 - 10.1080/01635580802357360
DO - 10.1080/01635580802357360
M3 - Article
C2 - 19116879
AN - SCOPUS:58149173326
VL - 61
SP - 94
EP - 102
JO - Nutrition and Cancer
JF - Nutrition and Cancer
SN - 0163-5581
IS - 1
ER -