Induction of apoptosis by all-trans retinoic acid in the human myeloma cell line RPMI 8226 and negative regulation of some of its typical morphological features by dexamethasone

Abstract

We investigated the effects of all-trans retinoic acid (RA) and dexamethasone (Dex) on the in vitro growth of the human myeloma cell line RPMI 8226. RA inhibited RPMI 8226 cell growth by both antiproliferative effect and induction of apoptosis. Typical morphological and biochemical characteristics of apoptosis including chromatin condensation, apoptotic bodies formation and internucleosomal DNA cleavage were detected after 4 days of treatment with 1 mM RA. In situ TUNEL assay demonstrated that DNA cleavage preceded chromatin condensation. The expression of tissue transglutaminase (tTG), an enzyme proposed to play a role in apoptosis was induced with RA, as shown by both enzymatic assay and in situ immunofluorescence detection. Dex, when used alone, had no effect on cell growth and apoptosis. When combined to RA, Dex did not interfere with the RA-dependent inhibition of cell proliferation, but unexpectedly inhibited both quantitatively and qualitatively several morphological and biochemical features of the apoptosis induced by RA. Dex did not affect RA-induced DNA breaks formation but impeded the progression of chromatin condensation and the formation of apoptotic bodies. Interestingly, Dex also inhibited the RAdependent induction of tTG. RU486, a glucocorticoid antagonist, counteracted all Dex effects. Taken together these data demonstrate that key cytoplasmic and nuclear events occurring during apoptosis are differentially regulated by RA and Dex in myeloma cell line RPMI 8226.

Effects of Dexamethasone, All-Trans Retinoic Acid, Vitamin D₃ and Interferon-α on FO Myeloma Cells

“…Although some steroid-like structures as medroxyprogesterone acetate have been shown to have a negative effect on stem cell apoptosis [14], most studies have shown that ATRA and dexamethasone had an apoptotic and antiproliferative effect on myeloma cell lines [15, 16]. It was also reported that dexamethasone and ATRA did not increase each other’s effect on apoptosis and cell counts [17]. …”

Increased expression of tissue‐type transglutaminase following middle cerebral artery occlusion in rats

“…The most potent inducers of TG‐2 are retinoids, which promote apoptosis in various cells including neurons (Ferrari et al . 1998; Lefebvre et al . 1999).…”

Intron-Exon Swapping of Transglutaminase mRNA and Neuronal Tau Aggregation in Alzheimer's Disease

“…It is induced in cultured cells by various agents including cytokines, such as interleukin-6 (IL-6) (1, 2), cyclic AMP (3-5), activation of the transcription factor, NFB (6 -8), and DNA methylation (9). The most potent inducers of tTG gene expression are retinoids (10 -12), which also promote apoptosis in various cells (13,14), including neurons (15-17).In this context, the history of tTG in Alzheimer's disease (AD) pathogenesis began almost 20 years ago with the report that brain tTG catalyzed cross-linking of neurofilament molecules (18). A decade later, A␤ peptide (19,20) as well as the ␤-amyloid precursor protein (21) were shown to be cross-linked by tTG.…”

“…It is induced in cultured cells by various agents including cytokines, such as interleukin-6 (IL-6) (1, 2), cyclic AMP (3-5), activation of the transcription factor, NFB (6 -8), and DNA methylation (9). The most potent inducers of tTG gene expression are retinoids (10 -12), which also promote apoptosis in various cells (13,14), including neurons (15-17).…”