Natarajan Nandakumar

Antioxidants and human diseases

Oxidative stress plays a pivotal role in the development of human diseases. Reactive oxygen species (ROS) that includes hydrogen peroxide, hyphochlorus acid, superoxide anion, singlet oxygen, lipid peroxides, hypochlorite and hydroxyl radical are involved in growth, differentiation, progression and death of the cell. They can react with membrane lipids, nucleic acids, proteins, enzymes and other small molecules. Low concentrations of ROS has an indispensable role in intracellular signalling and defence against pathogens, while, higher amounts of ROS play a role in number of human diseases, including arthritis, cancer, diabetes, atherosclerosis, ischemia, failures in immunity and endocrine functions. Antioxidants presumably act as safeguard against the accumulation of ROS and their elimination from the system. The aim of this review is to highlight advances in understanding of the ROS and also to summarize the detailed impact and involvement of antioxidants in selected human diseases.

Exposure to polycyclic aromatic hydrocarbons with special focus on cancer

ABSTRACT Polycyclic aromatic hydrocarbons (PAHs) are a group of compounds consisting of two or more fused aromatic rings. Most of them are formed during incomplete combustion of organic materials such as wood and fossil fuels, petroleum products, and coal. The composition of PAH mixtures varies with the source and is also affected by selective weathering effects in the environment. PAHs are ubiquitous pollutants frequently found in a variety of environments such as fresh water and marine sediments, the atmosphere, and ice. Due to their widespread distribution, the environmental pollution due to PAHs has aroused global concern. Many PAHs and their epoxides are highly toxic, mutagenic and/or carcinogenic to microorganisms as well as to higher forms of life including humans. The main aim of this review is to provide contemporary information on PAH sources, route of exposure, worldwide emission rate, and adverse effects on humans, especially with reference to cancer.

Kaempferol, a potential cytostatic and cure for inflammatory disorders

Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g., tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries, and grapes) and in plants or botanical products commonly used in traditional medicine (e.g., Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Its anti-oxidant/anti-inflammatory effects have been demonstrated in various disease models, including those for encephalomyelitis, diabetes, asthma, and carcinogenesis. Moreover, kaempferol act as a scavenger of free radicals and superoxide radicals as well as preserve the activity of various anti-oxidant enzymes such as catalase, glutathione peroxidase, and glutathione-S-transferase. The anticancer effect of this flavonoid is mediated through different modes of action, including anti-proliferation, apoptosis induction, cell-cycle arrest, generation of reactive oxygen species (ROS), and anti-metastasis/anti-angiogenesis activities. In addition, kaempferol was found to exhibit its anticancer activity through the modulation of multiple molecular targets including p53 and STAT3, through the activation of caspases, and through the generation of ROS. The anti-tumor effects of kaempferol have also been investigated in tumor-bearing mice. The combination of kaempferol and conventional chemotherapeutic drugs produces a greater therapeutic effect than the latter, as well as reduces the toxicity of the latter. In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of kaempferol with a focus on its molecular targets and the possible use of this flavonoid for the treatment of inflammatory diseases and cancer.

Mangiferin in cancer chemoprevention and treatment: pharmacokinetics and molecular targets.

Abstract A variety of bioactive food components have been shown to modulate inflammatory responses and to attenuate carcinogenesis. Polyphenols isolated several years ago from various medicinal plants now seem to have a prominent role in the prevention and therapy of a variety of ailments. Mangiferin, a unique, important, and highly investigated polyphenol, has attracted much attention of late for its potential as a chemopreventive and chemotherapeutic agent against various types of cancer. Mangiferin has been shown to target multiple proinflammatory transcription factors, cell- cycle proteins, growth factors, kinases, cytokines, chemokines, adhesion molecules, and inflammatory enzymes. These targets can potentially mediate the chemopreventive and therapeutic effects of mangiferin by inhibiting the initiation, promotion, and metastasis of cancer. This review not only summarizes the diverse molecular targets of mangiferin, but also gives the results of various preclinical studies that have been performed in the last decade with this promising polyphenol.

Anti-Oxidative Effect of Myrtenal in Prevention and Treatment of Colon Cancer Induced by 1, 2-Dimethyl Hydrazine (DMH) in Experimental Animals.

Colon cancer is considered as the precarious forms of cancer in many developed countries, with few to no symptoms; the tumor is often diagnosed in the later stages of cancer. Monoterpenes are a major part of plant essential oils found largely in fruits, vegetables and herbs. The cellular and molecular activities show therapeutic progression that may reduce the risk of developing cancer by modulating the factors responsible for colon carcinogenesis. Colon cancer was induced with DMH with a dose of (20 mg/Kg/body weight) for 15 weeks by subcutaneous injection once in a week. Myrtenal treatment was started with (230 mg/Kg/body weight) by intragastric administration, one week prior to DMH induction and continued till the experimental period of 30 weeks. The Invivo results exhibit the elevated antioxidant and lipid peroxidation levels in DMH treated animals. The Histopathological analysis of colon tissues well supported the biochemical alterations and inevitably proves the protective role of Myrtenal. Treatment with myrtenal to cancer bearing animals resulted in a remarkable increase in the inherent antioxidants and excellent modulation in the morphological and physiological nature of the colon tissue. It is thus concluded that myrtenal exhibits excellent free radical scavenging activity and anticancer activity through the suppression of colon carcinoma in Wistar albino rats.

Quorum sensing modulators exhibit cytotoxicity in Hodgkin’s lymphoma cells and interfere with NF-κB signaling

In recent years it has become evident that bacteria can modulate signaling pathways in host cells through the secretion of small signaling molecules. We have evaluated the cytotoxic effects and NF-κB inhibitory activities of a panel of quorum sensing molecules and their reactive analogs on Hodgkins lymphoma cells (L428). We found that several molecules inhibited NF-κB signaling in a dose dependent manner. Three inhibitors (ITC-12, ITC-Cl and Br-Furanone) showed 50% NF-κB inhibition at concentrations less than 10µM (4.1µM, 12.8µM and 9.9µM, respectively). Furthermore, all three molecules displayed cytotoxic effects against L428 cells with IC50 values of 12.4µM, 18.3µM and 3.1µM respectively after 48h incubation. They also showed inhibition of A549 adenocarcinoma cell migration at low concentrations 5.6µM, 2.6µM and 7.9µM respectively. Further analysis showed that these molecules significantly decrease the degree of expression of proteins of NF-κB subunits p50, p65 and RelB both in cytosolic and nuclear fractions. This confirms that these compounds have the potential to modulate the NF-κB pathway by suppressing their subunits and thus exhibit cytotoxicity and inactivation of NF-κB signaling in Hodgkins lymphoma cells.

Coral-associated bacterial extracts inhibit cellular NF-κB pathway

Abstract Marine natural products have recently been recognized as a promising source of NF-κB inhibitors. In this study, extracts of bacterial isolates from the coral Favis sp. were screened for NF-κB modulatory capability using an NF-κB luciferase reporter gene assay. The bacterial extracts had variable effects on NF-κB activity: from the 39 extracts tested, only one exhibited significant NF-κB inhibition and two caused NF-κB up regulation. In addition, we showed that coral bacteria New-33 extract inhibits NF-κB alternative pathway subunits in a non-cytotoxic manner. HPLC analysis confirmed the presence of a low molecular mass compound and NCBI megaBLAST revealed that the New-33 16S rRNA gene sequences are similar to Vibrio mediterranei. This specific modulation of the NF-κB by alternative pathway could contribute to therapeutic implications and also raises questions about host-symbiont interaction in the marine environment.