Disease relevance of NSC698299

• Zerumbone (ZER), a sesquiterpene from the edible plant Zingiber zerumbet Smith, has recently been found to suppress tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in a potent manner [1].
• A recent report shows that zerumbone (ZER) inhibits the proliferation of, and induces apoptosis in, colon cancer cells [2].
• Zerumbone (ZER), a sesquiterpene compound occurring in tropical ginger Zingiber zerumbet Smith, has been implicated as one of the promising chemopreventive agents against colon and skin cancer [3].
• Suppression of dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger sesquiterpene, and nimesulide: separately and in combination [4].
• Zerumbone, an anti-inflammatory phytochemical, induces expression of proinflammatory cytokine genes in human colon adenocarcinoma cell lines [5].

High impact information on NSC698299

• Zerumbone abolishes NF-kappaB and IkappaBalpha kinase activation leading to suppression of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion [6].
• As several genes that regulate proliferation and apoptosis are regulated by nuclear factor (NF)-kappaB, we hypothesized that zerumbone mediates its activity through the modulation of NF-kappaB activation [6].
• Overall, our results indicated that zerumbone inhibits the activation of NF-kappaB and NF-kappaB-regulated gene expression induced by carcinogens and that this inhibition may provide a molecular basis for the prevention and treatment of cancer by zerumbone [6].
• We recently showed that zerumbone, a sesquiterpene found in subtropical ginger, suppresses colonic tumor marker formation in rats and induces apoptosis in colon cancer cell lines [7].
• Histologic examination revealed that pretreatment(s) with zerumbone suppressed leukocyte infiltration and reduced proliferating cell nuclear antigen-labeling indices [7].

Biological context of NSC698299

• Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-unsaturated carbonyl group is a prerequisite [1].
• The cell cycle of HL-60 cells was observed after treatment with zerumbone, which induced G (2)/M cell cycle arrest in HL-60 cells in a time- and concentration-dependent manner, and decreased the cyclin B1/cdk 1 protein level [8].
• Zerumbone inhibited the growth of P-388D (1) cells, induced DNA fragmentation in culture, and significantly prolonged the life of P-388D (1)-bearing CDF (1) mice (ILS% = 120.5) at a dosage of 2 mg/kg [8].
• These findings might suggest possible chemopreventive ability of zerumbone, through suppression of COX-2 expression, cell proliferating activity of colonic mucosa, and induction of phase II detoxification enzymes in the development of carcinogen-induced ACF [9].
• The IC50 value of zerumbone (0.14 microM) is noticeably lower than those of the anti-tumor promoters we have hitherto obtained [10].

Anatomical context of NSC698299

• Zingiberaceous and citrus constituents, 1'-acetoxychavicol acetate, zerumbone, auraptene, and nobiletin, suppress lipopolysaccharide-induced cyclooxygenase-2 expression in RAW264.7 murine macrophages through different modes of action [11].
• Cell cycle arrest in HT-29 cells was observed at G0/G1 for 10 and 12.5 mM and G2/M for 25 mM after 24 h at concentrations of 10-25 mM of zerumbone, and a concentration-dependent increase in apoptosis (2-6% of viable cells) was observed after 48 h using the same concentration range [12].
• Expression of cyclooxygenase (COX)-2 in colonic mucosa exposed to AOM and/or zerumbone was also assayed [9].
• Zerumbone feeding significantly lowered the number of AgNORs in colonic crypt cell nuclei [9].
• Results of a previous pharmacological approach using specific inhibitors of mitogen-activated protein kinases (MAPKs) suggested that the activation of both c-Jun N-terminal kinase and extracellular signal-regulated protein kinase, however, not that of p38 MAPK, may be involved in zerumbone-induced IL-1beta expression pathways in Caco-2 cells [5].

Associations of NSC698299 with other chemical compounds

• In addition, we assessed the effects of zerumbone on cell proliferation activity of crypts by counting silver-stained nucleolar organizer regions protein (AgNORs) in colonic cryptal cell nuclei [9].
• Sesamol, vanillyl alcohol, and trans-ferulic acid exhibited moderate inhibitory actions on the Hsp60-induced cell proliferation; zerumbone, humulene, and caryophylene effectively inhibited it at low concentrations with IC(50) values of 529, 122, and 110 nM, respectively [13].

Gene context of NSC698299

• Zerumbone had no effect on those transcription factors, though it attenuated COX-2 mRNA expression, suggesting that it disrupts the stabilization of COX-2 mRNA [11].
• The present study was undertaken to explore the suppressive efficacy of zerumbone (ZER), a sesquiterpenoid present in the rhizome of Zingiber zerumbet Smith that is used as a condiment in Southeast Asian countries and known to be a potent suppressant of cyclooxygenase (COX)-2 and inducible nitric oxide synthase expression in cell culture systems [4].
• Surprisingly, zerumbone markedly induced the expression of interleukin (IL)-1alpha, IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha in each cell line in concentration- and time-dependent manners [5].
• Zerumbone ring-opening derivative 2 inhibited autophosphorylation of the essential histidine protein kinase (HPK), YycG, existing in Bacillus subtilis constituting a two-component system (TCS) [14].

References