Prodigiosin induces apoptosis of B and T cells from B-cell chronic lymphocytic leukemia

Abstract

We have previously reported that prodigiosin (2-methyl-3-pentyl-6-methoxyprodigiosene) induces apoptosis in human hematopoietic cancer cell lines with no marked toxicity in nonmalignant cell lines. In this study, we demonstrate that prodigiosin induces apoptosis of B-cell chronic lymphocytic leukemia (B-CLL) cells (n ¼ 32 patients). The dose-response for the cytotoxic effect of prodigiosin was analyzed in cells from 12 patients showing an IC 50 of 116725 nM. Prodigiosin induced apoptosis of B-CLL cells through caspase activation. We also analyzed the cytotoxic effect of prodigiosin in T cells from B-CLL samples and no differences were observed with respect to leukemia cells. This is the first report showing that prodigiosin induces apoptosis in human primary cancer cells.

Prodigiosin and its potential applications

“…Additionally, prodigiosin induced apoptosis in Jurkat and HL-60 cells that were deficient in p53 (Vogelstein et al 2000). These results suggested that prodigiosin induced apoptosis independently of p53 and DNA damage (Campàs et al 2003). Also, prodigiosins promoted H+/Cl-, a symport activity leading to acidification of the cytosol.…”

“…Other prodigiosins lack apoptotic activity, Prodigiosin is less toxic than fludarabine for normal T cells but exhibited similar effect in B-cell chronic lymphocytic leukemia (B-CLL) cells. Moreover, prodigiosin induced apoptosis in B-CLL cells that were resistant to treatment with fludarabine (Campàs et al 2003). Thus, these results suggested that inhibition of these signaling pathways could not explain the apoptotic activity of prodigiosins in B and T lymphocytes (Campàs et al 2003).…”

“…Moreover, prodigiosin induced apoptosis in B-CLL cells that were resistant to treatment with fludarabine (Campàs et al 2003). Thus, these results suggested that inhibition of these signaling pathways could not explain the apoptotic activity of prodigiosins in B and T lymphocytes (Campàs et al 2003). In vitro, prodigiosin was found to bind to DNA, assisting oxidative cleavage of double-strand DNA that correlated with cytotoxicity (Melvin et al 2000).…”

“…The mechanism by which prodigiosin bring out the apoptosis is unknown (Campàs et al 2003). Other prodigiosins lack apoptotic activity, Prodigiosin is less toxic than fludarabine for normal T cells but exhibited similar effect in B-cell chronic lymphocytic leukemia (B-CLL) cells.…”

The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic lymphocytic leukemia cells in vitro

“…[9][10][11][12] There has also been considerable interest in natural products active against CLL cells, including the green tea polyphenol epigallocatechin-3-gallate 13 and the bacterial metabolite prodigiosin. 14 The sesquiterpene lactone parthenolide (PTL) has been widely used in traditional medicine for the treatment of migraines and inflammation. 15 This compound has recently been shown to induce apoptosis of hepatoma 16,17 and cholangiocarcinoma 18 cell lines and of primary acute and chronic myeloid leukemia cells 19 in vitro, with IC 50 values varying between 5 and 20 mM.…”