curcumin and zerumbone

Cancer is the second leading cause of death in the world. Chemotherapy and radiotherapy (RT) are the common cancer treatments. In addition to these limitations, the development of adverse effects from chemotherapy and RT reduces the quality of life for cancer patients. Cellular radiosensitivity, or the ability to resist and overcome cell damage caused by ionizing radiation (IR), is directly related to cancer cells' response to RT. Therefore, radiobiological research is emphasizing chemical compounds 'radiosensitization of cancer cells so that they are more reactive in the IR spectrum. Recent years researchers have seen an increase in interest in natural products that have antitumor effects with minimal side effects. Natural products, on the other hand, are easy to recover and therefore less expensive. There have been several scientific studies done based on these compounds that have tested their ability in vitro and in vivo to induce tumor radiosensitization. The role of natural products in RT, as well as their usefulness and potential applications, is the goal of this current review.

Topics: Berberine; Biological Products; Curcumin; Emodin; Genistein; Humans; Neoplasms; Pentacyclic Triterpenes; Radiation-Protective Agents; Radiation-Sensitizing Agents; Radiotherapy; Resveratrol; Sesquiterpenes; Triterpenes; Ursolic Acid; Vitamin D; Withanolides

A regulated low level of nitric oxide (NO) production in the body is essential for maintaining homeostasis (neuroprotection, vasorelaxation, etc.), though certain pathophysiological conditions associated with inflammation involve de novo synthesis of inducible NO synthase (iNOS) in immune cells, including macrophages. A large body of evidence indicates that many inflammatory diseases, such as colitis and gastritis, as well as many types of cancer, occur through sustained and elevated activation of this particular enzyme. The biochemical process of iNOS protein expression is tightly regulated and complex, in which the endotoxin lipopolysaccharide selectively binds to toll-like receptor 4 and thereby activates its adaptor protein MyD88, which in turn targets downstream proteins such as IRAK and TRAF6. This leads to functional activation of key protein kinases, including IkB kinases and mitogen-activated protein kinases (MAPKs), such as p38 MAPK, JNK1/2, and ERK1/2, all of which are involved in activating key transcription factors, including nuclear factor-kappaB and activator protein-1. In addition, the production of proinflammatory cytokines such as interferon-gamma and interleukin-12 potentiates iNOS induction in autocrine fashions. Meanwhile, an LPS-stimulated p38 MAPK pathway plays a pivotal role in the stabilization of iNOS mRNA, which has the AU-rich element in its 3'-untranslated region, for rapid NO production. Thus, suppression and/or inhibition of the above-mentioned signaling molecules may have a great potential for the prevention and treatment of inflammation-associated carcinogenesis. In fact, there have been numerous reports of phytochemicals found capable of targeting NO production by unique mechanisms, including polyphenols, terpenoids, and others. This review article briefly highlights the molecular mechanisms underlying endotoxin-induced iNOS expression in macrophages, and also focuses on promising natural agents that may be useful for anti-inflammation and anticarcinogenesis strategies.

Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Antioxidants; Benzyl Alcohols; Catechin; Chemoprevention; Coumarins; Curcumin; Flavones; Mice; Nitric Oxide Synthase Type II; Rats; Resveratrol; Sesquiterpenes; Stilbenes

Biological, biochemical and physical stimuli activate inflammatory leukocytes, such as macrophages, resulting in induction and synthesis of proinflammatory proteins and enzymes, together with free radicals, as innate immune responses. On the other hand, chronic and dysregulated activation of some inducible enzymes, including NADPH oxidase (NOX), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, have been shown to play pivotal roles in the development of certain inflammatory diseases such as oncogenesis. While the use of synthetic agents, especially those targeting molecules, is an attractive and reasonable approach to prevent carcinogenesis, it should be noted that traditional herbs and spices also exist along with their active constituents, which have been demonstrated to disrupt inflammatory signal transduction pathways. In this mini-review, the molecular mechanisms of activation or induction of NOX, iNOS and COX-2, as well as some food phytochemicals with marked potential to regulate those key inflammatory molecules, are highlighted. For example, 1'-acetoxychavicol acetate, which occurs in the rhizomes of the subtropical Zingiberaceae plant, has been shown to attenuate NOX-derived superoxide generation in macrophages, as well as lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production through the suppression of iNOS and COX-2 synthesis, respectively. Notably, this phytochemical has exhibited a wide range of cancer prevention activities in several rodent models of inflammation-associated carcinogenesis. Herein, the cancer preventive potentials of several food phytochemicals targeting the induction of NOX, iNOS and COX-2 are described.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Benzyl Alcohols; Curcumin; Cyclooxygenase 2; Dinoprostone; Enzyme Induction; Enzyme Inhibitors; Food; Humans; Inflammation; Lipopolysaccharides; NADPH Oxidases; Nitric Oxide Synthase Type II; Plant Extracts; Sesquiterpenes; Terpenes

The anticancer properties of zerumbone (2,6,9 humulatriene-8-one, a sesquiterpenoid) from Zingiber aromaticum were compared with those of curcumin from Curcuma longa in an in vitro MTT tetrazolium salt assay using HT-29, CaCo-2, and MCF-7 cancer cells and in an azoxymethane (AOM)-induced animal model of colon cancer using aberrant crypt foci (ACFs) as a preneoplastic marker. The IC50 of zerumbone was approximately 10 mM and that of curcumin was 25 mM. 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. Male Sprague-Dawley rats were fed extracts in an AIN diet prepared from the equivalent of 4% by weight of dried rhizomes of Z. aromaticum and C. longa. ACFs were induced by two doses (15 mg/kg body weight) subcutaneously of AOM 1 wk apart, the rats were killed 10 wk later, and the ACFs were assessed in the colon. Total ACFs were significantly reduced by Z. aromaticum extract (down 21%, P < 0.05) relative to control, the effect being most evident with large ACFs (>3 aberrant crypts per focus). Similar reductions were observed with 4% C. longa extract in the diet (down 24%, P < 0.01) and with 2,000 ppm curcumin, the effect being particularly evident with large ACFs. The concentration of zerumbone in the Z. aromaticum extract diet was assayed at 300 ppm and of curcumin in the C. longa extract diet was also 300 ppm, i.e., the extract of C. longa was as effective at one-seventh the concentration of curcumin as the positive control. Zerumbone is effective as an anticancer agent, possibly by its apoptosis-inducing and antiproliferative influences. This latter possibility is currently being investigated.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Cell Cycle; Cell Division; Colonic Neoplasms; Curcumin; Dose-Response Relationship, Drug; Humans; Inhibitory Concentration 50; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Sesquiterpenes; Time Factors; Tumor Cells, Cultured; Zingiberaceae