Molecular and Cellular Biochemistry

, Volume 398, Issue 1–2, pp 147–156 | Cite as

Piperine inhibits IL-1β-induced IL-6 expression by suppressing p38 MAPK and STAT3 activation in gastric cancer cells

  • Yong Xia
  • Pham Ngoc Khoi
  • Hyun Joong Yoon
  • Sen Lian
  • Young Eun Joo
  • Kee Oh Chay
  • Kyung Keun Kim
  • Young Do Jung


Piperine, a kind of natural alkaloid found in peppers, has been reported to exhibit anti-oxidative and anti-tumor activities, both in vitro and in vivo. Interleukin-6 (IL-6) is an important cytokine that activates the signal transduction, promotes tumor cell metastasis, and induces malignancy, including in gastric cancer. However, the effects of piperine on IL-6 expression in gastric cancer cells have not yet been well defined. In this study, we investigated the effects of piperine on the IL-6 expression, and examined the underlying signaling pathways via RT-PCR, promoter studies and Western blotting in human gastric cancer TMK-1 cells. Our results showed that piperine inhibited interleukin-1β (IL-1β)–induced IL-6 expression in a dose-dependent manner. In addition, piperine also inhibited IL-6 promoter activity. Experiments with mitogen-activated protein kinase (MAPK) inhibitors and dominant negative mutant p38 MAPK indicated that p38 MAPK was essential for IL-6 expression in the TMK-1 cells. Additionally, signal transducer and activator of transcription 3 (STAT3) was also involved in the IL-1β-induced IL-6 expression in gastric cancer cells. Piperine inhibited IL-1β-induced p38 MAPK and STAT3 activation and, in turn, blocked the IL-1β-induced IL-6 expression. Furthermore, gastric cancer cells pretreated with IL-1β showed markedly enhanced invasiveness, which was partially abrogated by treatment with IL-6 siRNA, piperine, and inhibitors of p38 MAPK and STAT3. These results suggest that piperine may exert at least part of its anti-cancer effect by controlling IL-6 expression through the suppression of p38 MAPK and STAT3.


Piperine IL-6 Gastric cancer p38MAPK STAT3 


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yong Xia
    • 1
  • Pham Ngoc Khoi
    • 1
  • Hyun Joong Yoon
    • 1
  • Sen Lian
    • 1
  • Young Eun Joo
    • 1
  • Kee Oh Chay
    • 1
  • Kyung Keun Kim
    • 1
  • Young Do Jung
    • 1
    • 2
  1. 1.Research Institute of Medical SciencesChonnam National University Medical SchoolGwangjuRepublic of Korea
  2. 2.Department of BiochemistryChonnam National University Medical SchoolGwangjuRepublic of Korea

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