{"id":85226,"date":"2018-11-28T15:50:40","date_gmt":"2018-11-28T23:50:40","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2018\/11\/ancistrolikokine-e3-a-58%e2%80%b2-coupled-naphthylisoquinoline-alkaloid-eliminates-the-tolerance-of-cancer-cells-to-nutrition-starvation"},"modified":"2018-11-28T15:50:40","modified_gmt":"2018-11-28T23:50:40","slug":"ancistrolikokine-e3-a-58%e2%80%b2-coupled-naphthylisoquinoline-alkaloid-eliminates-the-tolerance-of-cancer-cells-to-nutrition-starvation","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2018\/11\/ancistrolikokine-e3-a-58%e2%80%b2-coupled-naphthylisoquinoline-alkaloid-eliminates-the-tolerance-of-cancer-cells-to-nutrition-starvation","title":{"rendered":"Ancistrolikokine E3, a 5,8\u2032-Coupled Naphthylisoquinoline Alkaloid, Eliminates the Tolerance of Cancer Cells to Nutrition Starvation"},"content":{"rendered":"<p style=\"padding-right: 20px\"><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/ancistrolikokine-e3-a-58e280b2-coupled-naphthylisoquinoline-alkaloid-eliminates-the-tolerance-of-cancer-cells-to-nutrition-starvation.jpg\"><\/a><\/p>\n<p>PANC-1 human pancreatic cancer cells are characterized by their ability to proliferate aggressively under hypovascular and hypoxic conditions in the tumor microenvironment, displaying a remarkable tolerance to nutrition starvation. The antiausterity strategy is a new approach in anticancer drug discovery aiming at the identification of potent agents that inhibit preferentially the survival of tumor cells during a limited supply of nutrients and oxygen. The new 5,8\u2032-coupled naphthyldihydroisoquinoline alkaloid ancistrolikokine E<sub>3<\/sub> (<b>4<\/b>), isolated from the Congolese liana <i>Ancistrocladus likoko<\/i>, showed potent preferential cytotoxicity against PANC-1 cells under nutrient-deprived conditions, with a PC<sub>50<\/sub> value of 2.5 \u03bcM, without exhibiting toxicity in normal, nutrient-rich medium. The compound was found to induce dramatic alterations in cell morphology, leading to cell death. Moreover, it inhibited significantly PANC-1 cell migration and colony formation in a concentration-dependent manner. This study on <b>4<\/b> provides the first live evidence of the effect of a naphthyldihydroisoquinoline alkaloid against PANC-1 cells in nutrient-deprived medium. Mechanistic investigations conducted suggest that compound <b>4<\/b> is a potent inhibitor of the activation of the Akt\/mTOR pathway. Furthermore, it inhibited the expression levels of the key autophagy regulators Atg5, Atg12, Beclin-1, LC3-I, and LC3-II. The results demonstrated that ancistrolikokine E<sub>3<\/sub> (<b>4<\/b>) is a potent early-stage inhibitor of the autophagy pathway in PANC-1 human pancreatic cancer cells. Ancistrolikokine E<sub>3<\/sub> (<b>4<\/b>) and related naphthylisoquinoline alkaloids are promising potential lead compounds for anticancer drug development based on the antiausterity strategy.<\/p>\n<p><!-- Link: <a href=\"https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.8b00733\">https:\/\/pubs.acs.org\/doi\/10.1021\/acs.jnatprod.8b00733<\/a> --><\/p>\n","protected":false},"excerpt":{"rendered":"<p>PANC-1 human pancreatic cancer cells are characterized by their ability to proliferate aggressively under hypovascular and hypoxic conditions in the tumor microenvironment, displaying a remarkable tolerance to nutrition starvation. The antiausterity strategy is a new approach in anticancer drug discovery aiming at the identification of potent agents that inhibit preferentially the survival of tumor cells [\u2026]<\/p>\n","protected":false},"author":444,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11],"tags":[],"class_list":["post-85226","post","type-post","status-publish","format-standard","hentry","category-biotech-medical"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/85226","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/444"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=85226"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/85226\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=85226"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=85226"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=85226"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}