In vitro effects of substance P analogue [d-arg1, d-phe5, d-trp79, leu11] substance P on human tumour and normal cell growth

Abstract

Analogues of the neurotransmitter substance P (SP) can interact with neuropeptide receptors, and are reported to inhibit growth of small cell lung cancer cell lines (SCLC CLs). We found [D-Arg1. D-Phe5. D-Trp7, 9. Leu11] substance P (D-Phe5SP) significantly inhibited DNA synthesis by 10 10 human tumour CLs; six SCLC. one N-SCLC (squamous), two ovarian and one squamous cervical carcinoma, with inhibition to 50° o control levels (IC50) of 20 - 50 µM. There was dose dependent inhibition of colony forming efficiency (CFE) in 3 3 SCLC and 1 1 N-SCLC CL. IC505 of 0. 5-6. 5 µM in 5°o serum. Exposure of SCLC CL HC12 to 100 µM D-Phe5SP for l-4h caused a progressive fall in viable cell number; surviving cells, grown in the absence of peptide, showed a decreased growth rate. During 1 weeks exposure of two SCLC CLs to 20 µM D-Ph5SP. growth was slower than control cultures, while 50-100 µM completely inhibited growth. These inhibitory effects were partially reversed by increasing serum concentration from 5 to 20° o. but not by SP. vasopressin, bombesin or insulin-like growth factor 1. There was some inhibition of CFE by 3 3 normal human bone marrows. IC505 of 30-80 µM. compared with 8 psi for HC12 in 20° o FCS. Therefore D-Phe5SP appears to have more potent antiproliferative effects in tumour cells than normal cells, suggesting a role for this analogue in tumour treatment. © Macmillan Press Ltd., 1992.