6-Shogaol from Dried Ginger Inhibits Growth of Prostate Cancer Cells Both In Vitro and In Vivo through Inhibition of STAT3 and NF-κB Signaling

Abstract

Despite much recent progress, prostate cancer continues to represent a major cause of cancer-related mortality and morbidity in men. Prostate cancer is the most common nonskin neoplasm and second leading cause of death in men. 6-Shogaol (6-SHO), a potent bioactive compound in ginger (Zingiber officinale Roscoe), has been shown to possess anti-inflammatory and anticancer activity. In the present study, the effect of 6-SHO on the growth of prostate cancer cells was investigated. 6-SHO effectively reduced survival and induced apoptosis of cultured human (LNCaP, DU145, and PC3) and mouse (HMVP2) prostate cancer cells. Mechanistic studies revealed that 6-SHO reduced constitutive and interleukin (IL)-6-induced STAT3 activation and inhibited both constitutive and TNF-a-induced NF-kB activity in these cells. In addition, 6-SHO decreased the level of several STAT3 and NF-kB-regulated target genes at the protein level, including cyclin D1, survivin, and cMyc and modulated mRNA levels of chemokine, cytokine, cell cycle, and apoptosis regulatory genes (IL-7, CCL5, BAX, BCL2, p21, and p27). 6-SHO was more effective than two other compounds found in ginger, 6-gingerol, and 6-paradol at reducing survival of prostate cancer cells and reducing STAT3 and NF-kB signaling. 6-SHO also showed significant tumor growth inhibitory activity in an allograft model using HMVP2 cells. Overall, the current results suggest that 6-SHO may have potential as a chemopreventive and/or therapeutic agent for prostate cancer and that further study of this compound is warranted. Cancer Prev Res; 7(6); 627-38. Ó2014 AACR.

Identification of a Dual Inhibitor of Janus Kinase 2 (JAK2) and p70 Ribosomal S6 Kinase1 (S6K1) Pathways

“…Various compounds in ginger have been reported to possess anti-cancer effects (27,28,36). We found gingerenone A and 6-shogaol to be the most potent among the tested ginger compounds.…”

Alantolactone selectively suppresses STAT3 activation and exhibits potent anticancer activity in MDA-MB-231 cells

“…STAT3 can trap constitutively activated NF-κB within the nucleus of cancer cells [32]. Maintaining NF-κB activity in tumors requires STAT3, which is constitutively activated as well [33]. In addition, both STAT3 and NF-κB activation induces changes in the expression of multiple target genes associated with survival, proliferation, and apoptosis, including Bcl-2, cyclin D1, and c-myc [34].…”

Extraction of Phytochemicals from Grains of Paradise Using Supercritical Carbon Dioxide

“…It effectively decreased survival and affected apoptosis process in human and mouse prostate cancer cells via inhibition of STAT3 and NF- activities. Compared with 6-paradol which found in grains of paradise seeds, 6-shogaol was more effective [8]. 6-shogaol may also prevent the growth of human pancreatic tumors and has a high responsive to gemcitabine by suppressing inflammatory pathways linked to tumorigenesis [9].…”