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Aquatic Plants Native to Asia and Australia
Published in Namrita Lall, Aquatic Plants, 2020
Marco Nuno De Canha, Danielle Twilley, B. Venugopal Reddy, SubbaRao V. Madhunapantula, N. P. Deepika, T. N. Shilpa, B. Duraiswamy, S. P. Dhanabal, Suresh M. Kumar, Namrita Lall
The 70% methanol extracts of N. officinale reduced the activity of matrix-metallo protease (MMP-9) in MDA-MB-231 human breast cancer. It was able to inhibit cell invasion by 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MDA-MB-231 cells and was able to decrease human colon carcinoma (HT115) cell invasion (Rose et al. 2005, Boyd et al. 2006). The aqueous extract of N. officinale reduced tumor growth in mice treated for 21 days with a dose of 0.5 g/ml using the Ehrlich tumor model (de Souza et al. 2016).
Endothelin and Cardiac Hypertrophy
Published in Malcolm J. Lewis, Ajay M. Shah, Endothelial Modulation of Cardiac Function, 2020
Biochemical mechanisms which link ET-1 receptors to the increase in transcriptional activity still remain to be elucidated. Recent studies have suggested that the putative second messenger system of α1-adrenergic stimulation, which is a classical hypertrophic factor for cardiomyocytes, is phospholipase C-mediated hydrolysis of phosphoinositide-4,5-biphosphate (PIP2), thereby leading to formation of inositol-1,4,5 triphosphate (IP3) and diacylglycerol (DG) (Ohtani et al., 1988). Endogenous DG as well as phorbol esters, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), increase synthesis of DNA and protein by activating protein kinase C (PKC) in adult rat cardiocytes (Claycomb et al., 1988), suggesting that their growth is mediated by PKC. It has been also reported that ET-1 stimulates mitogen-activated protein kinase (MAPK) and MAPK kinase activity in cultured cardiomyocytes (Bogoyevitch et al., 1993; Bogoyevitch et al., 1994). This signaling cascade may also be relevant to the hypertrophic response of the heart following PKC activation.
Efficacy, Safety, and Toxicological Aspects of Nutraceuticals
Published in Sheeba Varghese Gupta, Yashwant V. Pathak, Advances in Nutraceutical Applications in Cancer, 2019
Jayvadan K. Patel, Anita Patel
Concerning the photochemical, substantial attempt has been made to search for naturally arising compounds that may possibly helpful in the management of cancer (Kwon et al. 2007). Nexrutine is a commercially available herbal extract from the Phellodendron amurense. Isoquinoline alkaloids, phenolic compounds, and flavone glycosides are active constituents of nexrutine. A latest investigation discovered that nexrutine prevented the proliferation of lung and prostate cancer cells via the modulation of signal pathways mediated by Akt and cAMP response element binding; furthermore, its antiproliferative capabilities are analogous to those of berberine (James et al. 2011). In the mouse prostate model, nexrutine was found to be effectual against the initial stage of prostate tumor growth in addition to tumor succession in transgenic adenocarcinoma. Moreover, a recent study performed of stage II mouse skin tumorigenesis model demonstrated that nexrutine prevented the progress of skin tumorigenesis (Kumar et al. 2012). The similar group supplementary stated an antitumor effect in a tumorigenesis model of rat liver (Alam et al. 2015). In mice, only single dose of nexrutine before the use of 12-O-tetradecanoylphorbol 13-acetate (TPA) considerably reduced TPA-induced skin edema, hyperplasia, incorporation of thymidine, and activity of ornithine decarboxylase (Kumar et al. 2012).
Development of a nanotechnological hydrogel containing desonide nanocapsules in association with acai oil: design and in vivo evaluation
Published in Pharmaceutical Development and Technology, 2022
Priscila Rosa, Mariane Lago Friedrich, Juliana dos Santos, Natháli Schopf Pegoraro, Camila Camponogara, Sara Marchesan Oliveira, Cristiane de Bona da Silva, Andréa Inês Horn Adams
The antiedematogenic activity of the nanostructured hydrogels in an acute contact dermatitis model induced by croton oil was assessed. Croton oil contains 12-O-tetradecanoylphorbol-13-acetate (TPA) and other phorbol esters as main irritant agents (Saraiva et al. 2011). Its application triggers an inflammatory response characterized by edema, leading to increased vascular permeability, cell infiltration and proliferation, production of arachidonic acid metabolites, cytokines and other proinflammatory mediators (Patrick et al. 1987; Rao et al. 1993). A recognized immediate effect of TG includes vasoconstriction, which decreases the tissue edema, erythema and heat (Beltrani et al. 2005). Thus, our aim was to assess the antiedematogenic effect of the nanostructured hydrogels in a model of croton oil-induced skin inflammation, since it mimics several human skin diseases, such as psoriasis and atopic dermatitis (Sato et al. 2004; Pietrovski et al. 2011).
Ras-Mediated Activation of NF-κB and DNA Damage Response in Carcinogenesis
Published in Cancer Investigation, 2020
NF-κB controls the expression of several growth factors, oncogenes and tumor suppressor genes (c-myc, p53), genes encoding cell adhesion proteins (ICAM-1, Intercellular Adhesion Molecule 1; ELAM-1, Endothelial Leukocyte Adhesion Molecule 1; VCAM-1, Vascular Cell Adhesion Molecule 1) and proteases of the extracellular matrix (85–89). Studies have shown that NF-κB activity affects cell survival and determines the sensitivity of cancer cells to cytotoxic agents as well as ionizing radiation (90). NF-κB is activated by various stimuli, including growth factors, carcinogens and tumor promoters such as 12-O-tetradecanoylphorbol 13-acetate (TPA). The signal transduction pathways leading to NF-κB transcription factor activation have been extensively studied such as the MAP kinases (MAPK) family of proteins that include ERK1/2, JNK1/2, and P38 kinases (71–92). The MAPK are potently activated by stress such as UV, heat shock, and inflammation and play a major role in cell proliferation and transformation, apoptosis, cell survival, tumorigenesis, etc. (Figure 7). Studies have shown that MAPK are involved in the transcriptional activation of NF-κB (93–95). Therefore, the NF-κB pathway is a critical regulator of immune responses and is often dysregulated in cancer. Two NF-κB pathways have been described to mediate these responses, the canonical and the non-canonical.
Beneficial modulation of the tumor microenvironment and generation of anti-tumor responses by TLR9 agonist lefitolimod alone and in combination with checkpoint inhibitors
Published in OncoImmunology, 2019
Kerstin Kapp, Barbara Volz, Detlef Oswald, Burghardt Wittig, Matthias Baumann, Manuel Schmidt
Skin painting studies are frequently used as an experimental carcinogenesis model based on OCDE Guideline 451 “Carcinogenicity studies” and NTP Guideline “Specifications for the conduct of studies to evaluate the toxic and carcinogenic potential of chemical, biological and physical agents in laboratory animals for the National Toxicology Program”. The two-step skin carcinogenesis model is defined by an irreversible tumor initiation process that often involves the activation of the c-H-ras oncogene, and tumor promotion caused by topical application of a promoting test substance. One hundred and fifty outbreed female (hairless) SKH1 mice were grouped according to NTP-guidelines into three groups (50 mice each). A single dose of DMBA (7,12-Dimethylbenzanthracene) dissolved in acetone was applied to the back of each mouse (40 µg/mouse/application). As a promoter substance, TPA (12-O-tetradecanoylphorbol-13-acetate) was applied three times per week starting day 7. Lefitolimod (20 µg once-weekly) application was started in parallel and administered sc or ip in the respective group. Clinical observations, body weight, and skin tumors were recorded once a week. All surviving mice were sacrificed after 18 weeks. All mice sacrificed at that time and those that died during the application period were examined for skin tumors.