Inhibitory Effect of (2R)-1-(1-Benzofuran-2-yl)-N-propylpentan-2-amine on Lung Adenocarcinoma

Zsolt Mervai, Andrea Reszegi, Ildikó Miklya, József Knoll, Zsuzsa Schaff, Ilona Kovalszky, Kornélia Baghy

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)727-734
Number of pages8
JournalPathology and Oncology Research
Volume26
Issue number2
DOIs
Publication statusPublished - Apr 1 2020

Keywords

  • BPAP
  • Cancer
  • FVB/N
  • Geroconversion
  • Lung adenocarcinoma
  • Tumor inhibition

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Oncology
  • Cancer Research

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