zerumbone and Adenocarcinoma

Topics: Adenocarcinoma; Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Dogs; Down-Regulation; Drug Carriers; Female; Lipids; Mammary Neoplasms, Animal; Nanostructures; Sesquiterpenes; Signal Transduction; Up-Regulation

Zerumbone, a sesquiterpene occurring in zingiberaceous plants in Southeast Asian countries, has been shown to have anti-inflammatory effects in several independent experimental studies. We examined its effect on the expression of proinflammatory genes in human colon adenocarcinoma cell lines, Caco-2, Colo320DM, and HT-29, using reverse transcription-polymerase chain reaction (RT-PCR) assays. 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. 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. The present results imply that zerumbone increases the production of proinflammatory cytokines in cancerous tissues in the colon and that this biochemical property may cause side-effects.

Topics: Adenocarcinoma; Anti-Inflammatory Agents, Non-Steroidal; Cell Line, Tumor; Colonic Neoplasms; Cytokines; Gene Expression Regulation; Humans; Inflammation; Phytotherapy; Plant Extracts; Reverse Transcriptase Polymerase Chain Reaction; Sesquiterpenes

A recent report shows that zerumbone (ZER) inhibits the proliferation of, and induces apoptosis in, colon cancer cells. We suggest a mechanism for these phenomena, based on our recently proposed redox model of cell proliferation which stresses the importance of intracellular redox potential E in the control of proliferation of normal and cancer cells.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Division; Colonic Neoplasms; Fibroblasts; Fibrosarcoma; Glutathione; Humans; Neoplastic Stem Cells; Oxidation-Reduction; Phosphorylation; Phytotherapy; Protein Processing, Post-Translational; Retinoblastoma Protein; Sesquiterpenes; Structure-Activity Relationship

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. In the present study, we evaluated the anti-inflammatory and chemopreventive potentials of ZER in a variety of cell culture experiments. ZER effectively suppressed TPA-induced superoxide anion generation from both NADPH oxidase in dimethylsulfoxide-differentiated HL-60 human acute promyelocytic leukemia cells and xanthine oxidase in AS52 Chinese hamster ovary cells. The combined lipopolysaccharide- and interferon-gamma-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2, together with the release of tumor necrosis factor-alpha, in RAW 264.7 mouse macrophages were also markedly diminished. These suppressive events were accompanied with a combined decrease in the medium concentrations of nitrite and prostaglandin E(2), while the expression level of COX-1 was unchanged. ZER inhibited the proliferation of human colonic adenocarcinoma cell lines (LS174T, LS180, COLO205, and COLO320DM) in a dose-dependent manner, while the growth of normal human dermal (2F0-C25) and colon (CCD-18 Co) fibroblasts was less affected. It also induced apoptosis in COLO205 cells, as detected by dysfunction of the mitochondria transmembrane, Annexin V-detected translocation of phosphatidylserine, and chromatin condensation. Intriguingly, alpha-humulene, a structural analog lacking only the carbonyl group in ZER, was virtually inactive in all experiments conducted, indicating that the alpha,beta-unsaturated carbonyl group in ZER may play some pivotal roles in interactions with unidentified target molecule(s). Taken together, our results indicate that ZER is a food phytochemical that has distinct potentials for use in anti-inflammation, chemoprevention, and chemotherapy strategies.

Topics: Adenocarcinoma; Animals; Anticarcinogenic Agents; Apoptosis; Cell Division; Colonic Neoplasms; Cyclooxygenase 2; Free Radicals; Humans; Isoenzymes; Membrane Proteins; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Prostaglandin-Endoperoxide Synthases; Sesquiterpenes; Superoxides; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha