Role of interleukin-2 regulated proteins in immunosuppression by the N-alkylated prodigiosin analogue

Pandey, R.; Chander, Ramesh; Sainis, Krishna B.

doi:10.1016/j.intimp.2007.08.024

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…A decrease in their levels would suggest a block upstream in the G1 phase rather than an active effect of prodigiosin on these cell cycle proteins. Complete suppression of Cyclin D expression has been observed concanavalin A stimulated spleen cells in presence of MAMPDM [62] confirming that the blockage is during early G1 phase. This is further supported by no effect of UP or PNU on degradation of inhibitor of Cdk, p27 [60,61] and suppression of p27 and p21, negative regulators of cell proliferation, by prodigiosin [59].…”

Section: Role Of Cell Cycle Regulation In Anti-cancer Activity Of Prosupporting

confidence: 57%

“…Similar inhibition of cyclin E, Cdk 2, Cdk 4, phosphorylation of Rb has been reported in lymphocytes stimulated with phytohemataglutinin (PHA) in presence of UP or PNU [60,61]. Since in presence of these prodigiosins, the cells do not enter S phase and are arrested in G1 phase [57,[60][61][62] and these proteins are expressed at late G1 or in S phase, their inhibition is more likely to be consequence rather than cause for the proliferation inhibitory activity. A decrease in their levels would suggest a block upstream in the G1 phase rather than an active effect of prodigiosin on these cell cycle proteins.…”

Section: Role Of Cell Cycle Regulation In Anti-cancer Activity Of Promentioning

confidence: 60%

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Prodigiosins as Anti Cancer Agents: Living Upto Their Name

Pandey¹,

Chander²,

Sainis

2009

CPD

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Prodigiosins are a family of bright red colored bacterial pigment and derive their name from the miraculous (prodigious) events associated with their occurrence. They indeed seem to be living upto their name as a host of activities such as anti-microbial, anti-malarial, anti-cancer and immunosuppressive have been associated with them. Out of these, immunosuppressive and anti-cancer activity has received more importance as it has a clinical promise. Prodigiosins, isolated mostly from Gram negative bacteria are characterized by a common pyrryldipyrrylmethene structure with varying side chains. The review discusses the mechanisms involved in the anti-cancer activity of this class of compounds. In vitro, prodigiosins have been shown to primarily target the cancer cells independently of the p53 status while little or no effect has been observed on normal cells. In addition, prodigiosins are effective in cancer cells with multidrug resistance phenotype and defects in the apoptotic pathways. These make prodigiosins attractive candidates for further development. Though the molecular targets of prodigiosins have not been clearly defined, they have been found to target different signaling pathways possibly through induction of DNA double strand breaks and/ or neutralization of pH gradients leading to changes in cell cycle proteins and apoptosis. The review will discuss the recent findings related to the mechanism involved in the anti-cancer activity of this class of molecules.

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Section: Role Of Cell Cycle Regulation In Anti-cancer Activity Of Prosupporting

confidence: 57%

Section: Role Of Cell Cycle Regulation In Anti-cancer Activity Of Promentioning

confidence: 60%

Prodigiosins as Anti Cancer Agents: Living Upto Their Name

Pandey¹,

Chander²,

Sainis

2009

CPD

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“…This compound holds promise as a novel and effective ingredient in anticancer drug synthesis. The exact targets of Pg and its derivatives are not clearly defined, but their anticancer activity is believed to be closely related to the apoptosis process of cancer cells (Khanafari et al, 2006;Montaner et al, 2000;Pandey et al, 2007). Two derivatives of Pg, metacycloprodigiosin and undecylprodigiosin, have also been studied and shown to exhibit toxic activity against five human cancer cell lines including P388, HL-60, A-549, BEL-7402, and SPCA4.…”

Section: Introductionmentioning

confidence: 99%

Mutation of rsmC gene from Serratia marcescens QBN using CRISPR-Cas9 to enhance prodigiosin synthesis

Thanh,

Thi Thao,

Tuyen

et al. 2023

Vietnam J. Biotechnol.

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Prodigiosin is a bright red pigment, which is produced by various gram-negative and gram positive bacteria include S. marcescens, Hahella chejuensis, Vibrio psychroerythrus, Streptomyces coelicolor and many marine bacteria such as Pseudomonas sp, Vibrio sp. Prodigiosin has garnered considerable interest among the scientific community due to its immunosuppressive and anticancer properties against various drug-resistant cancer cell lines. In this study, we utilized the biosynthetic pathway of prodigiosin (Pg), using CRISPR/Cas9 gene editing techniques to eliminate the gene inhibiting Pg synthesis, known as rsmC, aiming to enhance the ability to synthesize Pg from S. marcescens strains. The rsmC gene of S. marcescens QBN was randomly mutated using the CRISPR-Cas9 system with the pCasPA vector (containing Cas9) and pCRISPR (carrying the spacer segment and sgRNA synthesis). A 20-nucleotide spacer segment was selected on rsmCpreceding the TGG triplet at the 3' end (PAM, the recognition site of Cas9) and inserted into pCRISPR between two BsaI sites. Following the binding of sgRNA to Cas9, mutations occurred in the nucleotides of the rsmC gene, resulting in the cleavage of the double-stranded DNA at the targeted site. A sequence homologous to the rsmC gene, lacking 100 nucleotides, was introduced into the cell and will involve the cleaved DNA's repair mechanism. The mutated rsmC strain of S. marcescens QBN synthesized Pg at 216 - 231 mg/L, higher than the original strain (180 mg/L). Furthermore, HPLC results and 1H spectral analysis showed that the synthesized red pigment from the mutated strain S. marcescens QBN was prodigiosin. These findings provide a basis for further improving the productivity of Pg synthesis in the S. marcescens QBN strain and serve as a basis for editing genes in other microorganisms using the CRISPR-Cas9 system.

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