|
|
Blood, 15 July 2005, Vol. 106, No. 2, pp. 690-697.
Prepublished online as a Blood First Edition Paper on March 31, 2005; DOI 10.1182/blood-2004-11-4273.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells
Traci E. Battle,
Jack Arbiser, and
David A. Frank
From the Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; and Department of Dermatology, Emory University School of Medicine, Atlanta, GA.
B-cell chronic lymphocytic leukemia (B-CLL) remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Honokiol is a natural product known to possess potent antineoplastic and antiangiogenic properties. We examined whether honokiol can overcome apoptotic resistance in primary tumor cells derived from B-CLL patients. Honokiol induced caspase-dependent cell death in all of the B-CLL cells examined and was more toxic toward B-CLL cells than to normal mononuclear cells, suggesting greater susceptibility of the malignant cells. Honokiol-induced apoptosis was characterized by the activation of caspase-3, -8, and -9 and cleavage of poly(adenosine diphosphate-ribose) polymerase (PARP). Exposure of B-CLL cells to honokiol resulted in up-regulation of Bcl2-associated protein (Bax) and down-regulation of the expression of the key survival protein myeloid-cell leukemia sequence 1 (Mcl-1), which is associated with response to treatment in B-CLL patients. In addition, B-CLL cells pretreated with interleukin-4 (IL-4), a cytokine known to support B-CLL survival, underwent apoptosis when subsequently incubated with honokiol, indicating that honokiol could also overcome the prosurvival effects of IL-4. Furthermore, honokiol enhanced cytotoxicity induced by fludarabine, cladribine, or chlorambucil. These data indicate that honokiol is a potent inducer of apoptosis in B-CLL cells and should be examined for further clinical application either as a single agent or in combination with other anticancer agents. (Blood. 2005;106:690-697)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. M. Raja, S. Chen, P. Yue, T. M. Acker, B. Lefkove, J. L. Arbiser, F. R. Khuri, and S.-Y. Sun
The natural product honokiol preferentially inhibits cellular FLICE-inhibitory protein and augments death receptor-induced apoptosis
Mol. Cancer Ther.,
July 1, 2008;
7(7):
2212 - 2223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Garcia, Y. Zheng, C. Zhao, A. Toschi, J. Fan, N. Shraibman, H. A. Brown, D. Bar-Sagi, D. A. Foster, and J. L. Arbiser
Honokiol Suppresses Survival Signals Mediated by Ras-Dependent Phospholipase D Activity in Human Cancer Cells
Clin. Cancer Res.,
July 1, 2008;
14(13):
4267 - 4274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E.-R. Hahm, J. A. Arlotti, S. W. Marynowski, and S. V. Singh
Honokiol, a Constituent of Oriental Medicinal Herb Magnolia officinalis, Inhibits Growth of PC-3 Xenografts In vivo in Association with Apoptosis Induction
Clin. Cancer Res.,
February 15, 2008;
14(4):
1248 - 1257.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E.-R. Hahm and S. V. Singh
Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity
Mol. Cancer Ther.,
October 1, 2007;
6(10):
2686 - 2695.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Li, W. Han, Y. Gu, S. Qiu, Q. Lu, J. Jin, J. Luo, and X. Hu
Honokiol Induces a Necrotic Cell Death through the Mitochondrial Permeability Transition Pore
Cancer Res.,
May 15, 2007;
67(10):
4894 - 4903.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-Z. Qin, H. Xin, L. A. Sitailo, M. F. Denning, and B. J. Nickoloff
Enhanced Killing of Melanoma Cells by Simultaneously Targeting Mcl-1 and NOXA
Cancer Res.,
October 1, 2006;
66(19):
9636 - 9645.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Ahn, G. Sethi, S. Shishodia, B. Sung, J. L. Arbiser, and B. B. Aggarwal
Honokiol Potentiates Apoptosis, Suppresses Osteoclastogenesis, and Inhibits Invasion through Modulation of Nuclear Factor-{kappa}B Activation Pathway
Mol. Cancer Res.,
September 1, 2006;
4(9):
621 - 633.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
