caa a22 4500 606235019 CHVBK 20210128101240.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2214-0 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2214-0 Piperine inhibits IL-1β-induced IL-6 expression by suppressing p38 MAPK and STAT3 activation in gastric cancer cells [Elektronische Daten] [Yong Xia, Pham Khoi, Hyun Yoon, Sen Lian, Young Joo, Kee Chay, Kyung Kim, Young 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. Springer Science+Business Media New York, 2014 Piperine nationallicence IL-6 nationallicence Gastric cancer nationallicence p38MAPK nationallicence STAT3 nationallicence Xia Yong Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut Khoi Pham Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut Yoon Hyun Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut Lian Sen Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut Joo Young Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut Chay Kee Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut Kim Kyung Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut Jung Young Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 147-156 0300-8177 398:1-2<147 2015 398 11010 https://doi.org/10.1007/s11010-014-2214-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2214-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Xia Yong Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut NATIONALLICENCE 700 1- Khoi Pham Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut NATIONALLICENCE 700 1- Yoon Hyun Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut NATIONALLICENCE 700 1- Lian Sen Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut NATIONALLICENCE 700 1- Joo Young Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut NATIONALLICENCE 700 1- Chay Kee Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut NATIONALLICENCE 700 1- Kim Kyung Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut NATIONALLICENCE 700 1- Jung Young Research Institute of Medical Sciences, Chonnam National University Medical School, 501-190, Gwangju, Republic of Korea aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 147-156 0300-8177 398:1-2<147 2015 398 11010