Different susceptibilities of human melanoma and breast carcinoma cell lines to retinoic acid-induced growth inhibition
Lotan, R.
Cancer Research 39(3): 1014-1019
1979
ISSN/ISBN: 0008-5472 PMID: 427741 Document Number: 148816
The ability of retinoic acid to inhibit the growth of 10 cell lines derived from human malignant tumors (6 melanomas and 4 breast carcinomas) and 2 cell lines derived from nonmalignant breast tissue was investigated in vitro. After a 7 day incubation in the presence of 10-6 M retinoic acid, the growth of the melanoma cell lines A375 and Hs939 was inhibited by 69 and 62%, respectively; the growth of lines Hs695, Hs852 and SH-4 was not affected, while the growth of the melanoma cell line Hs294 was stimulated 2-fold. Breast carcinomas cell lines SK-BR-3 and 734B were inhibited by 83 and 50%, respectively; cell line Hs578T was only slightly inhibited (28%) and the growth of line MDA-MB-157 was not affected. The growth of the nonmalignant mammary cell line HBL-100 was slightly inhibited (13%), and that of Hs578Bst was not affected. Further studies, carried out with the more sensitive cell lines (< 50% growth inhibited) revealed that the inhibitory effects of retinoic acid were dose dependent. The concentrations of retinoic acid required for 50% growth inhibition of cell lines SK-BR-3, A375, Hs939 and 734B were 1 .times. 10-9, 2.5 .times. 10-8, 1 .times. 10-7 and 3 .times. 10-7 M, respectively. When exposed to 10-6 M retinoic acid, the cells grew at a rate similar to that of control cells for 48 or 72 h, after which their growth rate decreased. Thus, the population-doubling times of A375, Hs939 and 734B in log phase growth increased from 32, 30 and 67 h to 48, 75 and 180 h, respectively. The growth of SK-BR-3 cells was arrested after exposure to retinoic acid for longer than 48 h. The morphology of all melanoma cells exposed to 10-6 M retinoic acid was not changed significantly, the breast carcinomas 734B and SK-BR-3 cells spread and assumed a flattened morphology after 72 h in the presence of retinoic acid. Cell lines derived from tumors of similar histopathological type differ in their responsiveness to retinoic acid.