期刊
JOURNAL OF IMMUNOLOGY
卷 178, 期 1, 页码 111-121出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.178.1.111
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- NCI NIH HHS [CA 92372] Funding Source: Medline
- NIAID NIH HHS [AI 21490] Funding Source: Medline
- NIA NIH HHS [AG 05731] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P01CA092372] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI021490] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG005731] Funding Source: NIH RePORTER
Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.
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