# Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells

## TL;DR

This paper introduces two new drugs that exploit cancer cell metabolism to trigger cell death through mitochondrial apoptosis.

## Contribution

The novel contribution is the development of two new drug compounds that induce mitochondrial apoptosis in cancer cells.

## Key findings

- Compound 1 and compound 3 inhibit the growth of 60 human cancer cell lines to nearly 0%.
- The drugs induce mitochondrial apoptosis by reactivating p53 and reducing cyclin D1.
- They also increase the cell cycle inhibitor p21Waf1/p21Cip1 in cancer cells.

## 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 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.