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In preclinical study, the phenanthrene derivative PJ34 exclusively eradicates human pancreatic cancer cells in xenografts


Prof. Malka Cohen-Armon and her team at Tel Aviv University's Sackler Faculty of Medicine choose Oncotarget for a third time amongst leading medical journals like The New England Journal of Medicine, Nature or The Lancet to publish groundbreaking preclinical cancer research.

Here's more: Recent reports demonstrate an exclusive eradication of a variety of human cancer cells by the modified phenanthridine PJ34. The efficient eradication of malignant cells in human pancreatic cancer xenografts presents a new model of pancreas cancer treatment.

Prof. Malka Cohen-Armon from the Sackler Faculty of Medicine & the Sagol School of Neuroscience at Tel-Aviv University in Tel-Aviv, Israel said, "Despite a substantial advance in cancer treatment, pancreatic ductal adenocarcinoma (PDAC) have a limited response to current treatments, and a low 5-years survival rate of about 6%."

Figure 1: Mitosis arrest preceding cell death in human PANC1 cells treated with PJ34. PANC1 cells, 24 hours after seeding, were incubated with PJ34 at the indicated concentrations. Changes in PANC1 cells ploidy were monitored by flow cytometry (Methods). The effect of PJ34 on the percentage of cells at each ploidy state (indicating the kinetics of S-phase entry and G2/M transition and sub-G1-dead cells) is quantitated by this method. Piled-up cells in double ploidy state after 48–72 hours incubation with PJ34 indicates cell-cycle arrest before or in mitosis. A massive cell death is measured after 120 hours incubation with PJ34.

Furthermore, the authors identified phenanthrenes acting as PARP1 inhibitors that efficiently eradicate a variety of human cancer cells without impairing benign cells.

However, their PARP1 inhibition per-se does not impair nor eradicate human malignant cells, including pancreatic cancer cells, PANC1.

In contrast, at higher concentrations than those causing PARP1 inhibition, PJ34, Tiq-A and Phen eradicate a variety of human cancer cells by mitotic catastrophe cell death.

Here, the efficacy of PJ34 to eradicate human pancreas cancer cells is tested in cell cultures and in xenografts.

In xenografts, eradication of human PANC1 cells deduced from a massive reduction of human proteins in the tumors was measured 30 days after the treatment with PJ34 has been terminated.

The Cohen-Armon Research Team concluded that PJ34, which is permeable in the cell membrane, accessed and eradicated human PDAC cells in xenografts without impairing normal proliferating cells infiltrated into the tumors. The team is 2-3 years away from clinical human trials.

Full text - https://doi.org/10.18632/oncotarget.27268

Correspondence to - Malka Cohen-Armon - marmon@tauex.tau.ac.il

Keywords - PJ34, pancreas cancer, stroma, PANC1 cancer xenografts

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