Curcumin inhibits interleukin 8 production and enhances interleukin 8 receptor expression on the cell surface:impact on human pancreatic carcinoma cell growth by autocrine regulation.
BACKGROUND
Curcumin, the yellow pigment in turmeric, has been shown to prevent tumor progression in a variety of tissues in rodents. The authors investigated the effect of curcumin on human carcinoma cell lines to determine whether constitutive interleukin-8 (IL-8) production of tumor cells was correlated with nuclear factor kappaB (NF-kappaB) activation and cell growth activity.


METHODS
A human pancreatic carcinoma cell line, SUIT-2, was incubated with various concentrations of curcumin for 2 hours. Biologic features, including IL-8 production, DNA binding activity, transactivation of NF-kappaB, cell growth activity, cell viability, and the expression of IL-8 receptors (CXCR1 and CXCR2) were analyzed.


RESULTS
The constitutive production of IL-8 was inhibited by curcumin at concentrations of 10-100 microM in a dose dependent manner. NF-kappaB activity was reduced significantly by curcumin treatment. Pretreatment with curcumin inhibited the growth rate of carcinoma cells significantly. Such cell growth inhibition by curcumin was not recovered by exogenous recombinant IL-8. The investigation of expression in IL-8 receptors, CXCR1 and CXCR2, revealed that the expression of both receptors was enhanced remarkably by curcumin. Exogenous IL-8 could not recover this enhancement of IL-8 receptors. These results suggest that curcumin inhibits IL-8-induced receptor internalization.


CONCLUSIONS
The authors concluded that curcumin contributed not only to the inhibition of IL-8 production but also to signal transduction through IL-8 receptors. These data suggest that curcumin reduces numerous IL-8 bioactivities that contribute to tumor growth and carcinoma cell viability. From this point of view, curcumin is a potent anticancer agent that inhibits the production of proinflammatory cytokines, including IL-8, by tumor cells.
Hidaka
Hideki
H
Department of Surgery I, Miyazaki Medical College, Japan.
Ishiko
Takatoshi
T
Furuhashi
Takashi
T
Kamohara
Hidenobu
H
Suzuki
Shunji
S
Miyazaki
Masashi
M
Ikeda
Osamu
O
Mita
Seiji
S
Setoguchi
Toshiaki
T
Ogawa
Michio
M
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D023062:Receptors, Interleukin-8A / Q000032:analysis*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D003474:Curcumin