-Shogaol attenuates inflammation, cell proliferation via modulate NF-κB and AP-1 oncogenic signaling in 7,12-dimethylbenz[a]anthracene induced oral carcinogenesis.
Biomed Pharmacother. 2017 Dec 26 ;98:484-490. Epub 2017 Dec 26. PMID: 29287195
Nuclear factor-kappaB (NF-κB) and activator protein 1 (AP-1) is a major transcription factor which regulates many biological and pathological processes such as inflammation and cell proliferation, which are major implicates in cancer progression. -Shogaol (-SHO) is a major constituent of ginger, exhibits various biological properties such as anti-oxidants, anti-inflammation and anti-tumor. Recently, we proven that -SHO prevents oral squamous cell carcinoma by activating proapoptotic factors in in vitro and in vivo experimental model. However, the preventive efficacy of -SHO in 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis (HBP) has not been fully elucidated, so far. Hence, we aimed to investigate the effect of -SHO on inflammation and cell proliferation by inhibiting the translocation of NF-κB and AP-1 in DMBA induced HBP carcinogenesis. In this study, we observed upregulation of inflammatory markers (COX-2, iNOS, TNF-α, interleukin-1 and -6), cell proliferative markers (Cyclin D1, PCNA and Ki-67) and aberrant activation of NF-κB, AP-1, IKKβ, c-jun, c-fos and decreased IκB-α in DMBA induced hamsters. Conversely, oral administration of -SHO strongly inhibited constitutive phosphorylation and degradation of IκB and inhibit phosphorylation of c-jun, c-fos, resulting in inhibition of nuclear translocation of NF-κBp65 and AP-1. Thus, inhibition of NF-κB and AP-1 activation by -SHO attenuates inflammation and cell proliferative response in DMBA induced hamsters. Our finding suggested that -SHO is a novel functional agent capable of preventing DMBA induced inflammation and cell proliferation associated tumorigenesis by modulating multiple signalling molecules.