{"id":905,"date":"2026-03-12T15:39:15","date_gmt":"2026-03-12T15:39:15","guid":{"rendered":"http:\/\/changingfaceofamerica.com\/?p=905"},"modified":"2026-03-12T15:39:15","modified_gmt":"2026-03-12T15:39:15","slug":"hdnc-suppresses-tnf-induced-nf-b-activation","status":"publish","type":"post","link":"https:\/\/changingfaceofamerica.com\/?p=905","title":{"rendered":"\ufeff== HDNC suppresses TNF- induced NF-B activation"},"content":{"rendered":"

\ufeff== HDNC suppresses TNF- induced NF-B activation.A,IL-8 expression. phosphorylation, both in cells in culture and in tumor xenografts. In addition, EMSA and luciferase reporter assays exhibited that HDNC significantly suppressed TNF–mediated activation and translocation of NF-B. This was further confirmed by western blot analysis of nuclear extracts wherein levels of RelA, the p65 component Cinnamic acid of NF-B was significantly less in cells treated with HDNC. Together, the data suggest that the novel compound HDNC (marmelin) is usually a potent anti-cancer agent that induces apoptosis during G1 phase of cell cycle and could be a potential chemotherapeutic candidate. Keywords:TNF-, chemotherapy, proliferation, apoptosis, marmelin == INTRODUCTION == Apoptosis is usually a genetically regulated form of cell death, in which abnormal cells are eliminated from an organism, ensuring normal development of multi-cellular organisms and maintenance of tissue homeostasis (1). Therefore an understanding of the molecular mechanisms of apoptosis is not only of scientific importance but may also have therapeutic value. A battery of signaling cascades are involved in the ability of cell to undergo apoptosis. One such is a family of cysteine proteases, caspases whose function in apoptotic cell death has been studied in detail (2), and are important mediators of apoptotic processes caused by various inducers (3). They amplify the apoptotic signal and proteolytically process numerous cellular target molecules with different functions (4). There are two major apoptotic pathways in mammalian cells (5,6). The extrinsic pathway is initiated by the binding of transmembrane death receptors (e.g., Fas, TNF-R1, and TRAIL receptors) with cognate extracellular ligands (7). Ligand receptors recruit adaptor proteins (e.g., TRADD, FADD), which interact with and trigger the activation of caspase 8. Activated caspase 8 then cleaves and activates downstream effector caspases such as caspase 3. In contrast, the intrinsic pathway is usually characterized by disruption of mitochondrial membrane integrity when cells are exposed to various stresses (e.g., DNA-damaging brokers) (8). Mitochondrial membrane integrity triggers apoptosis via both caspase-dependent (e.g., the cytochromec-caspase 9 pathway) and caspase-independent (e.g., the AIF pathway) mechanisms. Cross talk exists between the Cinnamic acid<\/a> extrinsic and intrinsic pathways, as activated caspase 8 can cleave Bid to produce truncated Bid (t-Bid), which then binds to mitochondria and promotes mitochondrial membrane integrity (9,10). The subsequent release of cytochromecfrom mitochondria further facilitates the apoptotic process (1113). The importance of cell signaling cascades in normal cell regulation and during disease condition have been realized (1416), and many well-known targets at the signaling levels have been identified that are critical Cinnamic acid for the ability of cancer cells to proliferate rapidly. Furthermore the availability of Cinnamic acid high throughput assays based the above said molecular targets has further Cinnamic acid enhanced the process of drug discovery (17). A majority of anticancer drugs are natural products or their semi-synthetic analogues; well known examples include taxol, epothilone, camptothecin, daunomycin and vinca alkaloids (18,19). Some of the herb derived anti-cancer compounds are beginning to enter clinical trials (19). Here we report the identification of a novel compound, 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde (HDNC) fromAegle marmelos, a medicinal herb from India used for treatment of cancer related symptoms in the Indian system of medicine (20). As a common term, we have named it marmelin. HDNC inhibits the growth of HCT-116 colon cancer cell tumor xenografts and angiogenesis in nude mice. In addition, HDNC suppresses cancer cell proliferation, while inducing apoptosis through the induction of activation of TNF, TNFRI, Rabbit Polyclonal to Musculin<\/a> TRADD, caspase-8, and t-Bid, resulting in cytochrome C release and activation of caspase-3. == MATERIALS AND METHODS == == Cells and reagents.<\/p>\n","protected":false},"excerpt":{"rendered":"

\ufeff== HDNC suppresses TNF- induced NF-B activation.A,IL-8 expression. phosphorylation, both in cells in culture and in tumor xenografts. In addition, EMSA and luciferase reporter assays exhibited that HDNC significantly suppressed TNF–mediated activation and translocation of NF-B. This was further confirmed by western blot analysis of nuclear extracts wherein levels of RelA, the p65 component Cinnamic […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[32],"tags":[],"class_list":["post-905","post","type-post","status-publish","format-standard","hentry","category-glycogen-phosphorylase"],"_links":{"self":[{"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=\/wp\/v2\/posts\/905","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=905"}],"version-history":[{"count":1,"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=\/wp\/v2\/posts\/905\/revisions"}],"predecessor-version":[{"id":906,"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=\/wp\/v2\/posts\/905\/revisions\/906"}],"wp:attachment":[{"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=905"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=905"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/changingfaceofamerica.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=905"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}