[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-327143-105":59,"doc-detail-327143-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","novel-antineoplastic-inducers-of-mitochondrial-apoptosis-in-human-cancer-cells","Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells","","I propose a strategy to suppress human cancer completely using two novel drug compounds that exploit the Warburg effect: defective mitochondrial aerobic respiration coupled with cytosolic aerobic fermentation/glycolysis of D-(+)-glucose to L-(+)-lactic acid. The drugs, compound 1 [P(op)T(est)162] and compound 3 (PT167), are highly symmetric, four-bladed propeller-shaped polyammonium cations. Compound 3 covalently combines compound 1 and compound 2 (PT166), a colchic(in)oid derivative of colchicine.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/novel-antineoplastic-inducers-of-mitochondrial-apoptosis-in-human-cancer-cells/327143/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/novel-antineoplastic-inducers-of-mitochondrial-apoptosis-in-human-cancer-cells/327143.png","ImageObject",300,407,{"name":92,"@type":93},"Anda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the proposed strategy to suppress human cancer in this work?","Question",{"text":112,"@type":113},"The work proposes two novel drug compounds that exploit the Warburg effect in cancer cells, targeting defective mitochondrial respiration and enhanced glycolysis to lactic acid.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How are compound 1 and compound 3 described chemically and functionally?",{"text":117,"@type":113},"Compound 1 is [P(op)T(est)162], and compound 3 (PT167) is a highly symmetric polyammonium cation that covalently combines compound 1 and compound 2 (PT166).",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism of cancer cell death is induced by the compounds?",{"text":121,"@type":113},"The compounds induce mitochondrial apoptosis involving cytochrome c release by (re)activating p53, which lowers dysregulated cyclin D1 and increases the cell-cycle inhibitor p21Waf1/Cip1.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},327143,1790164426,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962075006959,"https://ap-avatar.wpscdn.com/avatar/e0002397efbe92a78e?_k=1776741047341049297","molecules   \nArticle  \nNovel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells  \nAndreas J. Kesel   \nCitation: Kesel, A.J. Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells. Molecules 2024, 29, 914 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)molecules29040914  \nAcademic Editor: Wolfgang Sippl  \nReceived: 5 January 2024  \nRevised: 11 February 2024  \nAccepted: 14 February 2024  \nPublished: 19 February 2024  \nCopyright: © 2024 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nIndependent Researcher, Chammünsterstr. 47, D-81827 München, Bavaria, Germany; [andreasj.kesel@gmx.de](andreasj.kesel@gmx.de); Tel.: +49-(0)176-87974849  \nAbstract: I propose a new strategy to suppress human cancer completely with two entirely new drug compounds exploiting cancer’s Warburg effect characterized by a defective mitochondrial aerobic respiration, substituted by cytosolic aerobic fermentation/glycolysis of D-(+)-glucose into L-(+)-lactic acid. The two essentially new drugs, compound 1 [P(op)T(est)162] and compound 3 (PT167), represent new highly symmetric, four-bladed propeller-shaped polyammonium cations. The in vitro antineoplastic highly efficacious drug compound 3 represents a covalent combination of compound 1 and compound 2 (PT166) . The intermediate drug compound 2 is an entirely new colchic(in)oid derivative synthesized from colchicine. Compound 2’s structure was determined using X-ray crystallography. Compound 1 and compound 3 were active in vitro versus 60 human cancer cell lines of the National Cancer Institute (NCI) Developmental Therapeutics Program (DTP) 60-cancer cell testing. Compound 1 and compound 3 not only stop the growth of cancer cells to ±0%(cancerostatic effect) but completely kill nearly all 60 cancer cells to a level of almost −100%(tumoricidal effect) . Compound 1 and compound 3 induce mitochondrial apoptosis (under cytochrome c release) in all cancer cells tested by (re)activating (in most cancers impaired) p53 function, which results in a decrease in cancer’s dysregulated cyclin D1 and an induction of the cell cycle-halting cyclin-dependent kinase inhibitor p21Waf1 /p21Cip1 .  \nKeywords: cancer growth; tumor metastasis; cancer’s Warburg effect; p53; p53 (re)activators; mitochondrial apoptosis; cytochrome c release; tumoricidal drug effect  \n1. Introduction  \nAdenosine 5′ -triphosphate (ATP) is required for normal cell proliferation and survival and comes primarily from two sources. The first is glycolysis, which comprises a series of reactions that metabolizes D-(+)-glucose to pyruvate in the cytoplasm to produce anet of 2 molecules ATP from each D-(+)-glucose. The other is the citric acid cycle (CAC), also known as the Krebs cycle, Szent Györgyi−Krebs cycle or the tricarboxylic acid cycle (TCA cycle), which uses pyruvate formed from glycolysis in a series of reactions that donate electrons via nicotinamide adenine dinucleotide (NADH/H+ ) and flavin adenine dinucleotide (FADH 2) to the respiratory chain complexes in the mitochondria. With oxygen (O 2) serving as the final electron acceptor, electron transfer across the mitochondrial inner membrane creates a proton gradient, which forms in summary about 30–32 molecules ATP per one D-(+)-glucose molecule by catalysis of F 1FO–ATP synthase. In conditions of oxygen limitation, such as within muscles under prolonged exercise, pyruvate is not utilized in the citric acid cycle (CAC) but is converted into L-(+)-lactic acid (‘Fleischmilchsäure’) by lactate dehydrogenase (LDH) in a process termed anaerobic glycolysis.  \nIn 1930, Otto Heinrich Warburg (1883–1970) published [1] his theory on the origin of","cbCaib9VdRzSxk2Y","https://ap.wps.com/l/cbCaib9VdRzSxk2Y","pdf",49456107,43,"English","# Introduction\n## Cellular energy production and oxygen-limited glycolysis\n## Warburg hypothesis and Warburg effect\n## Glucose uptake and lactate production in tumors","[{\"question\":\"What is the proposed strategy to suppress human cancer in this work?\",\"answer\":\"The work proposes two novel drug compounds that exploit the Warburg effect in cancer cells, targeting defective mitochondrial respiration and enhanced glycolysis to lactic acid.\"},{\"question\":\"How are compound 1 and compound 3 described chemically and functionally?\",\"answer\":\"Compound 1 is [P(op)T(est)162], and compound 3 (PT167) is a highly symmetric polyammonium cation that covalently combines compound 1 and compound 2 (PT166).\"},{\"question\":\"What mechanism of cancer cell death is induced by the compounds?\",\"answer\":\"The compounds induce mitochondrial apoptosis involving cytochrome c release by (re)activating p53, which lowers dysregulated cyclin D1 and increases the cell-cycle inhibitor p21Waf1/Cip1.\"}]","Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells | PDF",1789976528,108]