Double-Strand DNA Cleavage by Copper·Prodigiosin

Melvin, Matt S.; Tomlinson, John T.; Saluta, Gilda; Kucera, Gregory L.; Lindquist, Niels; Manderville, Richard A.

doi:10.1021/ja0000798

Cited by 163 publications

(149 citation statements)

References 17 publications

(28 reference statements)

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“…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). DNA damage brought about the accumulation of p53 tumor suppressor protein (Vogelstein et al 2000), though, p53 was not induced by prodigiosin in B-CLL cells.…”

Section: Drawbacksmentioning

confidence: 95%

“…The lead prodiginine anticancer agent, Prodigiosin has been shown to intercalate into dsDNA. In the presence of copper, they promote oxidative cleavage of the DNA (Melvin et al 2000;Melvin et al 2002). This correlation between cytotoxicity and double -strand cleavage led to the hypothesis that cleavage of both strands of dsDNA is important for the proapoptotic anticancer activity of the prodiginines.…”

Section: Antibacterialmentioning

confidence: 99%

“…This correlation between cytotoxicity and double -strand cleavage led to the hypothesis that cleavage of both strands of dsDNA is important for the proapoptotic anticancer activity of the prodiginines. Prodigiosin has also been shown to bind by intercalation, preferentially at AT sequences, from the minor groove (Melvin et al 2000). The copper -mediated DNA cleavage of prodiginines inducing apoptosis, of cancer cells with little, or no, activity against nonmalignant cells has been explained by the availability of copper as cancer cells are reported to contain approximately 3.5 -fold higher concentrations of Cu(II) than nonmalignant cells.…”

Section: Antibacterialmentioning

confidence: 99%

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Prodigiosin and its potential applications

2015

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Since a decade, there has been a strong consumer demand for more natural products. This has augmented inclination towards substitution of synthetic colorants with natural pigments. Natural pigments not only have the capacity to increase the marketability of products, they also demonstrate valuable biological activities as antioxidants and anticancer agents. There is a long history of exploitation of natural products produced by bacteria as sources of pharmaceutically important, bioactive compounds. Among natural pigments, pigments from microbial sources are potentially suitable alternatives to synthetic pigments. The red pigment prodigiosin (PG) has unusual properties, which have long been documented. The red-pigmented prodiginines are bioactive secondary metabolites produced by both Gram-negative and Gram-positive bacteria. Prodigiosins are characterized by a common pyrrolyl pyrromethene skeleton, and the biological role of these pigments in the producer organisms remains unclear. Bacterial prodigiosins and their synthetic derivatives are effective proapoptotic agents against various cancer cell lines, with multiple cellular targets including multi-drug resistant cells with little or no toxicity towards normal cell lines. However, research into the biology of pigment production will stimulate interest in the bioengineering of strains to synthesize useful prodiginine derivatives. This review article highlights the characteristics and potential applications of prodigiosin pigment from Serratia as prodigiosins are real potential therapeutic drugs.

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Section: Drawbacksmentioning

confidence: 95%

Section: Antibacterialmentioning

confidence: 99%

Section: Antibacterialmentioning

confidence: 99%

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Prodigiosin and its potential applications

2015

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“…28 DNA damage induces the accumulation of p53 tumor suppressor protein. 16 However, p53 was not induced by prodigiosin in B-CLL cells.…”

Section: Prodigiosin Induces Apoptosis Of B-cll Cellsmentioning

confidence: 99%

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

et al. 2003

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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.

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13] Using the isocyanide carbon atom for synthesis of many cyclic systems in a formal…”

Section: Introductionmentioning

confidence: 99%