In vivo Study of a Newly Synthesized Chromen-4-one Derivative as an Antitumor Agent against HCC.

BACKGROUND: Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromene activity vary between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behaviors other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors, pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation, and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and anti-tumor activity. METHODS: In the present study, hepatocellular cancer (HCC) induced by diethylnitrosamine (DEN) in rats and then treated with the new chromene derivative and the parameters TNF-α, VEGF, p53, Cyt C, MMP-9, Bcl2, and Bax were measured. RESULTS: The treatment strategy Ch compound is to downregulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently control other factors such as p53, Cyt C, and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN-induced HCC in rats. CONCLUSION: The ability of the new Ch derivative to control the primary initiators of HCC such as TNF-α offers this derivative an anti-tumor activity and encourages further researches to follow and monitor its effect on the molecular level.

Samarium enriches antitumor activity of ZnO nanoparticles via downregulation of CXCR4 receptor and cytochrome P450.

Cancer is the leading cause of death and exhausts human and economic resources for treatment and protection. Zinc oxide nanoparticles play an effective role in tumor treatment but with some cautions, such as overexpression of cytochrome P450, hepatic overload, and the mammalian target of rapamycin pathway resistance. Although lanthanides have antitumor activity, their use is limited. Therefore, the current study aims to improve the effectiveness of zinc oxide nanoparticle via doping with lanthanides, such as samarium. In vitro study revealed that samarium doped with zinc oxide showed more antitumor activity than the other lanthanides, and the antitumor activity depends on the concentration of samarium in the nanocomposite. The in vivo experiment on mice bearing Ehrlich solid tumor revealed that intramuscular injection of samarium/zinc oxide downregulates the expressions of CXCR4 and PI3K/Akt/mammalian target of rapamycin pathway in respect to Ehrlich solid tumor group. Regarding the apoptotic biomarkers, samarium/zinc oxide upregulates the apoptotic biomarker; Bax accompanied with the mitotic catastrophe which was indicated by cell cycle arrest in G2 phase. Moreover, samarium:zinc oxide nanoparticles exhibited minimum toxicity which was indicated by suppressed activities of cytochrome P450 and hepatic enzymes, including alanine transaminase and aspartate transaminase. In addition, the histopathological finding, as well as immunophenotyping results, appreciated the biochemical finding. Therefore, samarium:zinc oxide might be offered a new approach to improve the effectiveness of zinc oxide nanoparticles along with lower toxic effect. Also, samarium:zinc oxide nanoparticles can be a candidate as a new antitumor compound to detect its mode of action.

Modulatory effect of a new benzopyran derivative via COX-2 blocking and down regulation of NF-κB against γ-radiation induced- intestinal inflammation.

Radiotherapy is considered as a primary modality for cancer treatment which accompanied by several side effects. Protection of normal tissues from radiation effects is one of the most significant concerns for researchers. Although many compounds acting as radio protectors, only two compounds were licensed clinically. Cyclooxygenase-2 (COX-2), as an inflammatory mediator is associated with ROS production with a NF-κB gene up regulation dependent manner in normal tissues. To that extend, his study was designed to target COX-2 and NF-κB by a newly synthesized benzopyran-4-one or chromone derivative; (2E)-2-((4-oxo-4H-chromen-3-yl) methylene amino-4- nitrobenzoic acid (Ch). Exposure of mice to IRR significantly induced intestinal inflammation via overexpression of COX-2 and NF-κB which is accompanied by an increase in the levels of MDA and iNOS in tissue homogenate and in the production of TNF-α and IL-6 as inflammatory signs. Moreover, the apoptotic effect of IRR was manifested by obvious elevation in caspase-3. Interapretonial injection of Ch significantly controls the inflammatory response by blocking the COX-2 and decrease the expression NF-κB which subsequently decreases other inflammatory parameters. Thus Ch compound might be a promising nonsteroidal anti-inflammatory drug (NSAID) against radiation-induced inflammation with a specific mode of COX-2 inhibition. Further researches are needed to elucidate its molecular mechanism and its combination with radiotherapy as a protector.

Immunomodulatory effect of new quinolone derivative against cisplatin/gamma radiation-induced renal and brain toxicity in mice.

Treatment of cancer often requires exposure to radiation, which has several limitations involving non-specific toxicity toward normal cells, reducing the efficacy of treatment. Recent studies synthesize new quinolone derivatives to satisfy other purposes such as treatment of inflammatory and malignant diseases. The main purpose of the present study is to evaluate the effect of a new quinolone derivative; 2-(1-Ethyl-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-2-oxoacetic acid (EHQA) and its possible mechanism against gamma radiation (IRR) and cisplatin (Cis) induced nephrotoxicity and neurotoxicity in mice. The structure of the newly synthesized quinolone derivative was elucidated by microanalytical and spectral data, which were found consistent with the assigned structures. Exposure to Cis and IRR significantly induced renal damage manifested by a significant increase in levels of urea and creatinine. Moreover, the exposure to both Cis and IRR significantly decreased the levels of anti-apoptotic protein; Bcl-2 in both renal and brain tissue homogenate accompanied by activation of an inflammatory marker; IL-17. Immunophenoting results showed an activation of T- lymphocytes marker; CD3 and B-lymphocytes marker; CD19. Interperitonial administration of EHQA significantly ameliorated the above-mentioned parameters. Overall, the present results indicated that EHQA is a promising anti-inflammatory and anti-apoptotic agent. From the obtained results it can be concluded that EHQA could be a candidate as immunomodulatory agents. Further studies are required to establish its molecular mechanism.