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BackgroundEmbelin, a quinone derivative, is found in the fruits of Embelia ribes Burm (Myrsinaceae). It has been shown to have a variety of therapeutic potentials including anthelmintic, anti-tumor, anti-diabetic, anti-bacterial and anti-inflammation. Inflammation is an immunological response to external harmful stimuli and is regulated by an endogenous pyrogen and pleiotropic pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α). TNF-α production has been implicated in a variety of other human pathologies including neurodegeneration and cancer. Several studies have shown that the anti-inflammatory activity of embelin is mediated by reduction in TNF-α. The latter is synthesized as a membrane anchored protein (pro-TNF-α); the soluble component of pro-TNF-α is then released into the extracellular space by the action of a protease called TNF-α converting enzyme (TACE). TACE, hence, has been proposed as a therapeutic target for inflammation and cancer.MethodsWe used molecular docking and experimental approaches to investigate the docking potential and molecular effects of embelin to TACE and human cancer cell characteristics, respectively.ResultsWe demonstrate that embelin is a potential inhibitor of TACE. Furthermore, in vitro studies revealed that it inhibits malignant properties of cancer cells through inactivation of metastatic signaling molecules including MMPs, VEGF and hnRNP-K in breast cancer cells.ConclusionBased on the molecular dynamics and experimental data, embelin is proposed as a natural anti-inflammatory and anticancer drug.

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Graphical abstract The etiology of the majority of human cancers is associated with a myriad of environmental causes, including physical, chemical, and biological factors. DNA damage induced by such mutagens is the initial step in the process of carcinogenesis resulting in the accumulation of mutations. Mutational events are considered the major triggers for introducing genetic and epigenetic insults such as DNA crosslinks, single- and double-strand DNA breaks, formation of DNA adducts, mismatched bases, modification in histones, DNA methylation, and microRNA alterations. However, DNA repair mechanisms are devoted to protect the DNA to ensure genetic stability, any aberrations in these calibrated mechanisms provoke cancer occurrence. Comprehensive knowledge of the type of mutagens and carcinogens and the influence of these agents in DNA damage and cancer induction is crucial to develop rational anticancer strategies. This review delineated the molecular mechanism of DNA damage and the repair pathways to provide a deep understanding of the molecular basis of mutagenicity and carcinogenicity. A relationship between DNA adduct formation and cancer incidence has also been summarized. The mechanistic basis of inflammatory response and oxidative damage triggered by mutagens in tumorigenesis has also been highlighted. We elucidated the interesting interplay between DNA damage response and immune system mechanisms. We addressed the current understanding of DNA repair targeted therapies and DNA damaging chemotherapeutic agents for cancer treatment and discussed how antiviral agents, anti-inflammatory drugs, and immunotherapeutic agents combined with traditional approaches lay the foundations for future cancer therapies.

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To understand the chemistry of Cu(II)-NH 3 -S(IV)-O 2 system, the kinetics of the oxidation of sulfur(IV) catalyzed by amminecopper(II) complexes has been studied in the ammonia-buffered solutions. Sulfur(IV) is oxidized to sulfate. The complexes, Cu(NH 3 ) 2+ , Cu(NH 3 ) 2+ 2 , and Cu(NH 3 ) 2+ 3 appear to be equally reactive and Cu(NH 3 ) 2+ 4 appears to be unreactive. The kinetics obey the rate law: 2+ 3 complexes, which appear to be equally reactive. The values of α 1 and γ 1 were found to be (1.32 ± 0.21) × 10 6 L 2 mol −2 s −1 (1.74 ± 0.40) × 10 9 L 3 mol −3 s −1 respectively at 30 • C. The reaction rate is not influenced by the presence of ethanol-a free radical scavenger, so a nonradical mechanism has been proposed. The results of this study are useful in understanding the atmospheric chemistry of aqueous phase autoxidation of dissolved sulfur dioxide in copper(II)-ammonia-sulfur(IV)-oxygen system at high pH. C