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Different susceptibilities of human melanoma and breast carcinoma cell lines to retinoic acid-induced growth inhibition.

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1979

Year

Abstract

The ability of retinoic acid to inhibit the growth of ten cell lines derived from human malignant tumors (six melanomas and four breast carcinomas) and two cell lines derived from nonmalignant breast tissue was investigated in vitro . After a seven-day incubation in the presence of 10−6 m retinoic acid, the growth of the melanoma cell lines A375 and Hs939 was inhibited by 68 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 two-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 × 10−9, 2.5 × 10−8, 1 × 10−7, and 3 × 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 hr, 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 hr to 48, 75, and 180 hr, respectively. The growth of SK-BR-3 cells was arrested after exposure to retinoic acid for longer than 48 hr. The morphology of all melanoma cells exposed to 10−6 m retinoic acid was not changed significantly; however, the breast carcinomas 734B and SK-BR-3 cells spread and assumed a flattened morphology after 72 hr in the presence of retinoic acid. These results demonstrate that cell lines derived from tumors of similar histopathological type differ in their responsiveness to retinoic acid.