Abstract
Several analogues of somatostatin were examined in the Mia PaCa-2 human pancreatic cancer cell line for their ability to promote tyrosine phosphatase activity affecting the receptors for the epidermal growth factor.
The inhibition of growth of the Mia PaCa-2 cells in culture was also evaluated to determine the mechanism of action of somatostatin analogues and their relative effectiveness in inhibiting cancer growth.
Of the analogues tested D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) caused the greatest stimulation of tyrosine phosphatase activity.
Analogue D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) had less effect but was more potent than somatostatin-14.
Analogue D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol) (SMS 201-995) produced no significant dephosphorylation.
The analogues displayed the same order of activity in assays on growth inhibition of Mia PaCa-2 cells in cultures. Analogue (SMS-201-995) caused virtually no tyrosine phosphatase stimulation or growth inhibition in this cancer cell line, although it possesses a much higher antisecretory activity than somatostatin-14 in normal tissues.
These observations indicate that somatostatin and some of its analogues can act as growth inhibitors in cancer cells through the activation of tyrosine phosphatase.
These data reinforce the view that somatostatin analogue RC-160 and related compounds could be used for treatment of pancreatic cancer.
See also:
- Official Web Site: The Di Bella Method;
- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;
- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);
- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);
- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);
- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);
- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);
- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;
- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;
- Neuroblastoma: Complete objective response to biological treatment;
- Oesophageal squamocellular carcinoma: a complete and objective response;