Abstract
This overview summarizes recent data disclosing the efficacy of the PARP inhibitor PJ34 in exclusive eradication of a variety of human cancer cells without impairing healthy proliferating cells. Its cytotoxic activity in cancer cells is attributed to the insertion of specific un-repairable anomalies in the structure of their mitotic spindle, leading to mitotic catastrophe cell death. This mechanism paves the way to a new concept of cancer therapy.
Highlights
In the last twenty years the modified phenanthridine PJ34 has been known for its activity as a PARP inhibitor [1,2] (Figure 1)
In mice subcutaneously injected with human MDA-MB-231 triple negative breast cancer cells (5 × 106 ), PJ34 slow release for 14 days prevented the development of tumors in three out of five mice, and those mice remained tumor-free during the following four months
ABT-888 neither arrested mitosis, nor eradicated the tested human cancer cells [31]. These findings suggested a possible interference of PJ34 with the construction of the mitotic spindle in the tested human cancer cells
Summary
In the last twenty years the modified phenanthridine PJ34 has been known for its activity as a PARP (polyADP-ribose polymerase) inhibitor [1,2] (Figure 1). Treatment with PARP inhibitors in BRCA mutant carriers is based on the interference of PARP1 inhibition with DNA repair in cells carrying a damaged DNA. Unlike other PARP inhibitors, these small molecules exclusively eradicated a variety of human cancer cells without affecting proliferating and non-proliferating healthy somatic cells. They did not affect human epithelial, mesenchymal and endothelial cells [28,29,30,31,32,33,34,35], nor healthy cells of mouse origin, including mouse embryonic fibroblasts (MEF), fibroblasts, neurons in the central nervous system and neuronal progenitor stem cells [28,29,31,32,33,34]. Mice treated with PJ34 for 2–3 weeks, continued to gain a similar amount of weight as untreated mice, and did not exert any visible stress or discomfort signs, as described below
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