Novel Antineoplastic Inducers of Mitochondrial Apoptosis in Human Cancer Cells.

I propose a new strategy to suppress human cancer completely with two entirely new drug compounds exploiting cancer's 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 [] and compound (), represent new highly symmetric, four-bladed propeller-shaped polyammonium cations. The in vitro antineoplastic highly efficacious drug compound represents a covalent combination of compound and compound (). The intermediate drug compound is an entirely new colchic(in)oid derivative synthesized from colchicine. Compound 's structure was determined using X-ray crystallography. Compound and compound 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 and compound 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 and compound induce mitochondrial apoptosis (under cytochrome 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 p21/p21.