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Antiproliferative effect of hormon analogs and small molecules in serum

Antiproliferative effect of hormon analogs and small molecules in serum

Antiproliferative effect of hormon analogs and small molecules in serum

 

Recent experimental data have shown that in addition to the indirect mechanism of action of growth hormone-releasing hormone (GHRH) antagonists through the inhibition of the pituitary GH/hepatic IGF-I axis they may also exert their antiproliferative effect on cancer cells directly. The direct effect of GHRH antagonists is mediated by the tumoral GHRH receptors identified in our laboratory, which is followed by an increase in cAMP level and calcium influx leading to apoptosis of cancer cells. Besides the hormon analogs, experimentally selected mixtures of certain small molecules (such as melatonin, vitamin D3) have also antiproliferative and apoptosis inducing effect on various cancer cells. However, the signalling pathways beyond these antiproliferative effects have been poorly understood. Therefore, first we intend to study the changes in gene expression profiles of LNCaP human prostate cancer cells and HELA human cervix carcinoma cells after treatments with GHRH antagonists and mixtures of small molecules, respectively. The cDNA microarray analysis would be followed by validation of selected gene expressions with quantitative RT-PCR.

Principal investigators

  • Zoltan Rekasi, MD, PhD, Dr. habil. (associate professor)
  • Tamas Czompoly, MD, PhD (head of laboratory, Culevit Ltd, Cancer Research and Drug Development Center)

Members of the group

  • Dalma Scheffer, PhD student
  • Magnus Maloy, MD, PhD student

Laboratory technician

  • Eniko Nagy

Key publications

  • Rekasi Z., Varga J. L., Schally A. V., Halmos G., Armatis P., Groot K., Czompoly T. (2000) Antagonists of growth hormone-releasing hormone and vasoactive intestinal peptide inhibit tumor proliferation by different mechanisms: evidence from in vitro studies on human prostatic and pancreatic cancers. Endocrinology, 141: 2120-2128.
  • Rekasi Z., Czompoly T., Schally A.V.,  Halmos G. (2000) Isolation and sequencing of cDNAs for splice variants of growth hormone-releasing hormone receptors from human cancers. Proc. Natl. Acad. Sci. USA, 97: 10561-10566.
  • Rekasi Z., Czompoly T., Schally A. V., Boldizsar F., Varga J. L., Zarandi M., Berki T.,  Horvath R. A., Nemeth P. (2005) Antagonist of growth hormone-releasing hormone induces apoptosis via a Ca2+-dependent pathway in LNCaP human prostate cancer cells. Proc. Natl. Acad. Sci. USA., 102: 3435-3440.
  • Toller G. L., Nagy E., Horvath R. A., Klausz B., Rekasi Z. (2006) Circadian expression of Bmal1 and serotonin-N-acetyltransferase mRNAs in chicken retina cells and pinealocytes in vivo and in vitro. J. Mol. Neurosci. 28: 143-150.                       
  • Rekasi Z., Horvath R. A., Klausz B., Nagy E., Toller G. L. (2006) Suppression of serotonin-N-acetyltransferase transcription and melatonin secretion from chicken pinealocytes transfected with Bmal1 antisense oligonucleotides containing locked nucleic acid in superfusion system. Mol. Cell. Endocrinol. 249: 84-91.
  • Scheffer D., Kulcsar Gy., Mezes B., Nagyeri Gy., Kiss-Merki M., Maloy M., Rekasi Z., Czompoly T. (2018) Cancer cell specific Induction of ER stress by a mixture of nutrient molecules.  Cancer Biother. Radiopharm. (submitted)
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