Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells

Andreas J. Kesel

doi:10.20944/preprints202401.0070.v2

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preprints.org > medicine and pharmacology > oncology and oncogenics > doi: 10.20944/preprints202401.0070.v2

Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells

Andreas J. Kesel

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)

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 p21^Waf1/p21^Cip1.

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.

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Comments (1)

Comment 1

Received: 4 January 2024
Commenter: Andreas Kesel
Commenter's Conflict of Interests: Author

Comment: New editing of Figure 11, Figure 13 and Figure 15, and of the Graphical Abstract. The original Figures given in version 1 (v1) of the Article were not optimal in resolution and final appearance. The manuscript text was not changed, only Figure 11, Figure 13, Figure 15 and the Graphical Abstract.

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