BPAP is a potent enhancer substance with catecholaminergic and serotoninergic activity
in the brain. It was discovered that it is also effective against certain types of
experimental cancers, showing the most promising results in case of lung cancer. That
is why we tested its efficacy in two different doses in a newly developed EGFR wild
type mouse lung adenocarcinoma xenograft model. Experiments were conducted on FVB/N
and SCID mouse strains treated with low and high dose of BPAP. Body weight, survival,
and tumor volumes were recorded. Furthermore, the activity of major signaling pathways
of NSCLC such as MAPK and Akt/mTOR as well as cell cycle regulation were determined.
Significant inhibition of tumor growth was exerted by both doses, but the mechanism
of action was different. High dose directly inhibited, whereas low dose activated
the main signaling pathways. Exposure to low dose BPAP resulted in elevated activity
of the mTOR pathway together with p16INK-induced cell cycle arrest, a typical feature
of geroconversion, a senescent state characterized by loss of cell proliferation.
Finally the events culminated in cell cycle inhibition point in case of both doses
mirrored by the decrease of cyclin D1, CDK4 and PCNA. In addition, BPAP treatment
had a beneficial effect on bodyweight suggesting that the compound at least in part
is able to compensate the cancer-related wasting. In view of the low toxicity and
confirmed antitumor effect of BPAP against experimental lung adenocarcinoma, this
novel compound deserves further attention.
