Retinoic acid inhibits the growth of human myeloma cells in vitro

Retinoic acid has been shown to induce growth inhibition in a variety of cell types including human myeloma cell lines. Bone marrow plasma cells from 31 multiple myeloma (MM) patients were cultured to investigate the activity of 13-cis-retinoic acid (cRA), all-trans-retinoic acid (tRA), interferon-α (IFN-α), interferon-γ (IFN-γ), and dexamethasone (DEX), alone or in combination, on in vitro proliferation and immunoglobulin (Ig) secretion. Both cRA and tRA inhibited proliferation: the labelling index (LI) of treated cultures/controls, was 0.47±0.05 (mean ± standard error mean, M ± SEM) P < 0.0001, and 0.67 ± 0.04 (M ± SEM), P < 0.0001, respectively. The inhibitory effect of cRA was significantly superior to tRA ( P = 0.0129) and IFN-α, similar to IFN-γ and DEX. The combinations of cRA + IFNα, tRA + IFN-γ, tRA + DEX did not show any synergistic effect on myeloma proliferation. In contrast, the combination cRA + DEX (0.29 ± 0.04, M±SEM) markedly increased the effect of both cRA and DEX used as single agents.
Ig synthesis was not significantly affected by CRA, tRA, IFN-γ and the combination tRA + IFN-γ, As expected, only IFN-α ( P 0.002) and DEX ( P 0.001) inhibited Ig production. The combinations cRA + IFN-α, cRA-DEX and tRA + DEX decreased Ig secretion to the same extent as IFN-α and DEX alone respectively. In conclusion, our data indicate that tRA and especially cRA strongly inhibited plasma cell proliferation but had no effect on Ig synthesis. The combination of cRA + DEX showed the highest degree of inhibitory activity of all cytokines. alone or in combination.