Luteolin inhibits protein kinase Cε and c-Src activities and UVB-induced skin cancer

Sanguine Byun, Ki Won Lee, Sung Keun Jung, Eun Jung Lee, Mun Kyung Hwang, Sung Hwan Lim, Ann M. Bode, Hyong Joo Lee, Zigang Dong

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Abstract

Luteolin, a flavonoid present in various vegetables including onion and broccoli, has been reported to possess anticarcinogenic effects. However, its chemopreventive effect on UV-induced skin cancer and its mechanism are not fully understood. Herein, we examined the chemopreventive effect and associated mechanisms of luteolin in the JB6 P+ cell line and the SKH-1 hairless mouse model. Luteolin suppressed UVB-induced cyclooxygenase-2 expression and activator protein-1 and nuclear factor-κB activity in JB6 P+ cells. Immunoblot and kinase assay data showed that luteolin attenuated protein kinase Cε (PKCε) and Src kinase activities and subsequently inhibited UVB-induced phosphorylation of mitogen-activated protein kinases and the Akt signaling pathway. In addition, pull-down assays revealed that luteolin binds directly to PKCε and Src in an ATP-competitive manner. Importantly, luteolin suppressed tumor incidence, multiplicity, and overall size in SKH-1 hairless mice. Analysis of the skin by immunohistochemistry and immunoblotting showed that luteolin-treated groups had a substantial reduction in the levels of cyclooxygenase-2, tumor necrosis factor-α, and proliferating cell nuclear antigen compared with groups treated with only UVB. Further analysis using skin lysates showed that luteolin inhibited PKCε and Src kinase activity. Together, these data suggest that luteolin exerts potent chemopreventive activity against UVB-induced skin cancer mainly by targeting PKCε and Src.

Original languageEnglish
Pages (from-to)2415-2423
Number of pages9
JournalCancer Research
Volume70
Issue number6
DOIs
Publication statusPublished - 2010 Mar 15

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Byun, S., Lee, K. W., Jung, S. K., Lee, E. J., Hwang, M. K., Lim, S. H., Bode, A. M., Lee, H. J., & Dong, Z. (2010). Luteolin inhibits protein kinase Cε and c-Src activities and UVB-induced skin cancer. Cancer Research, 70(6), 2415-2423. https://doi.org/10.1158/0008-5472.CAN-09-4093