Article
Version 1
Preserved in Portico This version is not peer-reviewed
Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells
Version 1
: Received: 31 December 2023 / Approved: 2 January 2024 / Online: 3 January 2024 (02:17:22 CET)
Version 2 : Received: 3 January 2024 / Approved: 3 January 2024 / Online: 4 January 2024 (09:34:19 CET)
Version 2 : Received: 3 January 2024 / Approved: 3 January 2024 / Online: 4 January 2024 (09:34:19 CET)
A peer-reviewed article of this Preprint also exists.
Kesel, A.J. Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells. Molecules 2024, 29, 914. Kesel, A.J. Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells. Molecules 2024, 29, 914.
Abstract
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 for 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 by 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 both 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 of cancer's dysregulated cyclin D1 and an induction of the cell cycle-halting cyclin-dependent kinase inhibitor p21Waf1/p21Cip1.
Keywords
cancer growth; tumor metastasis; cancer's Warburg effect; p53; p53 (re)activators; mitochondrial apoptosis; cytochrome c release; tumoricidal drug effect
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments (0)
We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.
Leave a public commentSend a private comment to the author(s)
* All users must log in before leaving a comment