Study Shows the Eradication of Cancer Cells by the Modified Phenanthridine PJ34

A recent cancer study led by Tel Aviv University (TAU) could induce the destruction of pancreatic cancer cells, indicates the potency of PJ34 to cause a substantial eradication of pancreas cancer cells in xenografts. 

In addition to the measured moderate change in PANC1 tumors’ size in one mouse (mouse # 19) the tumor started to shrink after 3 weeks of daily treatments with PJ34 and disappeared on day 56 of the TAU study published on October 22, 2019.

This is a limited, but important finding, since pancreatic cancer, is currently resistant to all treatments, and patients have poor chances of surviving for 5 years after being diagnosed.

Pancreatic cancer accounts for about 3 percent of all cancers in the US and about 7 percent of all cancer deaths, says the American Cancer Society (ACS). Its estimates for pancreatic cancer in the USA for 2019 are:

• About 56,770 people (29,940 men and 26,830 women) will be diagnosed with pancreatic cancer.
• About 45,750 people (23,800 men and 21,950 women) will die of pancreatic cancer.

Furthermore, this TAU study reported 30 days after the treatment with PJ34 had been terminated, an 80–90 percent reduction in human proteins in the tumors had been measured.

Their small quantities are attributed to the eradication of the human PANC1 cancer cells, the only human cells in the xenografts. 

Immuno-histochemistry performed in slices of all PANC1 tumors revealed the massive reduction in immunolabeled human proteins in the tumors developed in mice treated with PJ34, without affecting an abundant protein in fibroblasts infiltrated into the tumors.

Thus, eradication of human PANC1 cells in the xenografts is deduced from the reduction in the measured (with a high statistical significance) immuno-labeling of three arbitrarily selected human proteins in PANC1 tumors developed in mice treated with PJ34, compared to their immunolabeling in tumors of untreated mice.

A similar reduction in immuno-labeled human proteins was measured in a patient-derived pancreas cancer xenografts.

The enhanced necrosis in PANC1 tumors developed in mice treated with PJ34 supports cell eradication in these tumors.

Eradication of PANC1 cells in the tumors is also in line with PJ34-evoked cell death of PANC1 cells.

An abundantly expressed protein in fibroblasts infiltrated in the PANC1 tumors was not affected in mice treated with PJ34.

A substantial volume of pancreas tumors is occupied by stroma. Thus, the exclusive eradication of PANC1 cells in the xenografts could be screened by un-affected cells in the stroma, causing a discrepancy between the modest reduction in the volume of PANC1 tumors developed in PJ34 treated mice versus the substantial reduction of PANC1 cells in these tumors.

According to the present results, PJ34 does not seem to harm the wellbeing of the treated mice or their weight gain. 

In support, MTD (maximal tolerance dose) experiment performed with immunocompetent BALB/C mice IV injected with higher doses of PJ34 did not exert morbidity or mortality, nor indicated any abnormal clinical signs in the mice or their weight gain.

An additional advantage of the treatment with PJ34 is its potency to inhibit matrix metalloproteinases, which may decrease the chances to develop metastases.

In conclusion, according to these results, a small molecule that prevents the clustering of NuMA in the mitotic spindle poles of human cancer cells efficiently eradicates PDAC cells. 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 exclusive cytotoxicity of PJ34 in human cancer cells offers a new model of pancreas cancer therapy which does not impair normal tissues.

This study was led by Prof. Malka Cohen-Armon and her team at TAU’s Sackler Faculty of Medicine, in collaboration with Dr. Talia Golan’s team at the Cancer Research Center at Sheba Medical Center.

This research team did not specifically study whether or not the treatment could prolong the lifespan of a pancreatic cancer patient.

The work was funded by an ICRF grant and a donation of American Friends of Tel Aviv University. No conflicts were disclosed by these researchers.

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