A longevity study with enhancer substances (selegiline, BPAP) detected an unknown tumor-manifestation-suppressing regulation in rat brain

J. Knoll, K. Baghy, S. Eckhardt, P. Ferdinandy, M. Garami, L. G. Harsing, P. Hauser, Z. Mervai, T. Pocza, Z. Schaff, D. Schuler, I. Miklya

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aims First proof to show that (−)-deprenyl/selegiline (DEP), the first selective inhibitor of MAO-B, later identified as the first β-phenylethylamine (PEA)-derived synthetic catecholaminergic activity enhancer (CAE) substance and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP), the tryptamine-derived presently known most potent, selective, synthetic enhancer substance, are specific markers of unknown enhancer-sensitive brain regulations. Main methods Longevity study disclosing the operation of tumor-manifestation-suppressing (TMS) regulation in rat brain. Immonohistochemical identification of a fibromyxosarcoma in rats. Experiments with human medulloblastoma cell lines. Analysis of the mechanism of action of enhancer substances. Key findings Whereas 20/40 saline-treated rats manifested a fibromyxosarcoma, in groups of rats treated with 0.001 mg/kg DEP: 15/40 rats; with 0.1 mg/kg DEP: 11/40 rats (P < 0.01); with 0.0001 mg/kg BPAP: 8/40 rats (P < 0.001); with 0.05 mg/kg BPAP: 7/40 rats (P < 0.01) manifested the tumor. Experiments with human medulloblastoma cell lines, HTB-186 (Daoy); UW-228-2, showed that BPAP was devoid of direct cytotoxic effect on tumor cells, and did not alter the direct cytotoxic effectiveness of temozolomide, cisplatin, etoposide, or vincristine. Interaction with distinct sites on vesicular monoamine-transporter-2 (VMAT2) is the main mechanism of action of the enhancer substances which clarifies the highly characteristic bi-modal, bell-shaped concentration-effect curves of DEP and BPAP. Significance Considering of the safeness of the enhancer substances and the finding that DEP and BPAP, specific markers of unknown enhancer sensitive brain regulations, detected the operation of an enhancer-sensitive TMS-regulation in rat brain, it seems reasonable to test in humans low dose DEP or BPAP treatment against the spreading of a malignant tumor.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalLife Sciences
Volume182
DOIs
Publication statusPublished - Aug 1 2017

Fingerprint

Selegiline
Rats
Tumors
Brain
Neoplasms
Medulloblastoma
temozolomide
Cells
Vesicular Monoamine Transport Proteins
Phenethylamines
Cell Line
Monoamine Oxidase
Vincristine
Etoposide
Cisplatin
Amines

Keywords

  • (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP)
  • Enhancer substances
  • Enhancer-sensitive tumor-manifestation-suppressing (TMS) regulation
  • Fibromyxosarcoma
  • Selegiline/(−)-deprenyl

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

A longevity study with enhancer substances (selegiline, BPAP) detected an unknown tumor-manifestation-suppressing regulation in rat brain. / Knoll, J.; Baghy, K.; Eckhardt, S.; Ferdinandy, P.; Garami, M.; Harsing, L. G.; Hauser, P.; Mervai, Z.; Pocza, T.; Schaff, Z.; Schuler, D.; Miklya, I.

In: Life Sciences, Vol. 182, 01.08.2017, p. 57-64.

Research output: Contribution to journalArticle

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AU - Garami, M.

AU - Harsing, L. G.

AU - Hauser, P.

AU - Mervai, Z.

AU - Pocza, T.

AU - Schaff, Z.

AU - Schuler, D.

AU - Miklya, I.

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