Inhibitory Effects of Retinoic Acid or Retinyl Acetate on the Growth of Untransformed, Transformed, and Tumor Cells In Vitro

Abstract

The ability of vitamin A derivatives (“retinoids”) to inhibit the growth of 31 untransformed, transformed, or tumor celliines was investigated in vitro. Two retinoids, retinyl acetate and, to a greater extent, retinoic acid (10⁻⁵ M), inhibited the growth of certain transformed and tumor cells. According to their sensitivity to these retinoids, cells were divided into the following categories: a) cells not affected (<10% inhibition) or only slightly inhibited (<25%) by retinoids, such as untransformed CHO-K1-pro, BHK, and Balb/3T3 cells, virally transformed SV3T3 (simian virus 40-transformed), MSV3T3 (murine sarcoma virus-transformed), and PyBHK (polyoma virus-transformed), chemically transformed BP3T3 (benzo[a]pyrene-transformed), lymphosarcoma RAW8, and the human fibrosarcoma HT1080; b) cells that were growth inhibited (25–50%), such as neuroblastoma C1300, mouse mammary adenocarcinomas M12 and DD3, human breast carcinosarcoma H_S0578, and the murine lymphomas S49 and EL4; c) cells that were moderately growth inhibited (50–75%), such as mouse sarcoma S180, mastocytoma P815, mammary adenocarcinoma Mm5mT, myeloma S194, lymphoma BW5147, and rat mammary adenocarcinoma R3230AC; and d) cells that were extremely sensitive to retinoids (growth inhibited >75%), such as murine melanomas B16 and S91, rat mammary adenocarcinomas 13762NF and DMBA#8, murine lymphosarcoma RAW117 and myeloma P3, human lymphoid cell line RPMI 1788, and Burkitt's lymphoma (DAUDI). The findings showed that the growth of a considerable number of transformed and tumor cells could be inhibited in vitro by retinoids and suggested that the previously observed antitumor activity of retinoids in vivo is at least partly due to direct inhibition of cell proliferation.