A. Orosz et al., NEW SHORT-CHAIN ANALOGS OF A SUBSTANCE-P ANTAGONIST INHIBIT PROLIFERATION OF HUMAN SMALL-CELL LUNG-CANCER CELLS IN-VITRO AND IN-VIVO, International journal of cancer, 60(1), 1995, pp. 82-87
Human small-cell lung-cancer cells (SCLC) produce and secrete gastrin-
releasing peptide (GRP), the mammalian equivalent of bombesin (BN). Th
ere is some evidence to suggest that CRP is an autocrine regulator of
SCLC cell growth. In the search for potent BN antagonists, several sub
stance-P (SP) analogs were found to inhibit the growth of SCLC cells.
We found that a known short-chain SP antagonist, pHOPA-DTrp-Phe-DTrp-L
eu-Leu-NH2 (NY3238), inhibits the binding of I-125-Tyr(4)-BN on Swiss
3T3 cell line expressing BN receptors, as well as the proliferation of
NCI-H69 SCLC cells. In this study we tested several analogs of NY3238
and we found that NY3521 and NY3460 ave more effective in inhibition
of proliferation of SCLC cells but less potent in inhibition of bindin
g of I-125-Tyr(4)-BN on Swiss 3T3 cells than NY3238. Furthermore, we d
etected specific binding of radiolabelled NY3238 even below I nM on NC
I-H69 cells that could have been inhibited by SP and NY3460 rather tha
n by BN. In addition to these in vitro studies, NY3460 proved to be ef
fective in inhibiting the growth of NCI-H69 SCLC xenografts in nude mi
ce in vivo. These analogs of NY3238 could be promising therapeutic age
nts in the treatment of SCLC.(C) 1995 Wiley-Liss, Inc.