Somatostatin analogue octreotide and melatonin inhibit bromodeoxyuridine incorporation into cell nuclei and enhance apoptosis in the transplantable murine colon 38 cancer.
There is much evidence of the antiproliferative activity of somatostatin (SS) and melatonin (Mel) upon the normal and neoplastic tissues. It has also been found, that both substances are able to alter, under certain conditions, apoptotic processes. Recently, it has been postulated that apoptosis plays a pivotal role in the control of tumour growth. So far, there is no data about the effect of SS analogue--octreotide (Sandostatin, SMS) and Mel on the apoptosis of colon cancer cells. The aim of this study is to examine the effects of SMS and Mel administered separately or together on apoptosis, bromodeoxyuridine incorporation and weight of tumours in the murine transplantable Colon 38 cancer. The male mice were implanted subcutaneously (s.c.) with a suspension of Colon 38 cells. After 6 days, the animals were subcutaneously injected with SMS, Mel, SMS and Mel together (once daily at 6-8 p.m., for 6 days). The incorporation of bromodeoxyuridine (BrDU) into cell nuclei was used as an index of cell proliferation (labelling index-LI). The in situ labelling of nuclear DNA fragmentation according to TUNEL method was considered as an apoptotic index (AI). Given separately, both SMS and Mel significantly decreased the LI and increased the AI. However, we have not observed any additive effect of SMS and Mel on either BrDU incorporation or apoptosis. The mean AI in the group treated jointly with SMS and Mel was significantly lower than in groups treated separately with SMS or Mel. It was also found, that the proliferation/apoptosis ratio were significantly lower in the group treated with SMS or MEL, which means that the imbalance between these two processes changed in favour of cell death. Possibly, the observed antitumour effects of these two substances could be due to this alteration.
Mełen-Mucha
G
G
Institute of Endocrinology, Medical University of Lódz, Poland.
Winczyk
K
K
Pawlikowski
M
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D004354:Drug Screening Assays, Antitumor; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015282:Octreotide / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D018931:Antineoplastic Agents, Hormonal; D001973:Bromodeoxyuridine; D008550:Melatonin; D015282:Octreotide