Upgrade of chrysomycin A as a novel topoisomerase II inhibitor to curb KRAS-mutant lung adenocarcinoma progression

Zhang, Junmin; Liu, Pei; Chen, Jianwei; Liu, Qing; Zhang, Jilei; Zhang, Huawei; Leung, Elaine Lai‐Han; Yao, Xiaojun; Liu, Liang

doi:10.1016/j.phrs.2022.106565

Cited by 6 publications

(3 citation statements)

References 78 publications

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“…IRD-009 HCT-116 cells (colorectal cancer) Cell cycle modulator (G 0 /G 1 phase arrest), induction of apoptosis via DNA double strand interaction and damage [ 92 ] Prodigiosin Tripyrrole Pigment Serratia marcescens MDA-MB-231 cells and xenograft (breast cancer), MDA-MB-468 cells (breast cancer) Induction of apoptosis and downregulation of HSP90α. Suppression of migration and invasion and induction of apoptosis and via inhibition of Wnt/ β-catenin signaling [ 93 , 94 ] Pyocin S2 Bacteriocin Pseudomonas aeruginosa HepG2 cells (hepatocellular carcinoma), IM-9 cells (B-lymphoblastoid cell line) Induction of cell death [ 95 ] Pyocyanin Phenazine Pigment Pseudomonas aeruginosa MCF7 cells (breast cancer) Induction of apoptosis and necrosis [ 96 ] Rebeccamycin/NSC 655649 Indocarbozole Lechevalieria aerocoloigenes, Saccharothrix aerocolonigenes P388 cells (leukemia), L1210 cells (leukemia), B16 tumor model (melanoma), A549 xenograft (lung adenocarcinoma), Intercalates with DNA, promotes double strand breakage, inhibits topoisomerase I [ 97 , 98 ] Resistomycin Pentacyclic Polyketide Antibiotic Streptomyces aurantiacus AAA5 HepG2 cells (hepatocellular carcinoma), HeLa cells (cervical cancer), MDA-MB-231 xenograft (breast cancer), patient derived xenograft (breast cancer) Induction of cell death. Suppression of tumor progression, metastasis, and invasion by Pellino-1 inhibition and SNAIL/SLUG degradation [ 99 , 100 ] Salinomycin Carboxylic Polyether Ionophore Streptomyces albus OVCAR-8 (ovarian cancer), mammary cancer stem cells, patient -derived CLL cells Induction of apoptosis and G1 cell cycle arrest via Skp2 destabilization and Stat...…”

Section: Emerging Anticancer Agents From Microbial Metabolitesmentioning

confidence: 99%

Redefining bioactive small molecules from microbial metabolites as revolutionary anticancer agents

Giurini,

Godla,

Gupta

2024

Cancer Gene Ther

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Cancer treatment remains a significant challenge due to issues such as acquired resistance to conventional therapies and the occurrence of adverse treatment-related toxicities. In recent years, researchers have turned their attention to the microbial world in search of novel and effective drugs to combat this devastating disease. Microbial derived secondary metabolites have proven to be a valuable source of biologically active compounds, which exhibit diverse functions and have demonstrated potential as treatments for various human diseases. The exploration of these compounds has provided valuable insights into their mechanisms of action against cancer cells. In-depth studies have been conducted on clinically established microbial metabolites, unraveling their anticancer properties, and shedding light on their therapeutic potential. This review aims to comprehensively examine the anticancer mechanisms of these established microbial metabolites. Additionally, it highlights the emerging therapies derived from these metabolites, offering a glimpse into the immense potential they hold for anticancer drug discovery. Furthermore, this review delves into approved treatments and major drug candidates currently undergoing clinical trials, focusing on specific molecular targets. It also addresses the challenges and issues encountered in the field of anticancer drug research and development. It also presents a comprehensive exposition of the contemporary panorama concerning microbial metabolites serving as a reservoir for anticancer agents, thereby illuminating their auspicious prospects and the prospect of forthcoming strides in the domain of cancer therapeutics.

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Section: Emerging Anticancer Agents From Microbial Metabolitesmentioning

confidence: 99%

Redefining bioactive small molecules from microbial metabolites as revolutionary anticancer agents

Giurini,

Godla,

Gupta

2024

Cancer Gene Ther

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“…A-419 [1]. It had been demonstrated CA possesses remarkable antimicrobial activity against Mycobacterium tuberculosis (MT), multidrug-resistant (MDR) tuberculosis and methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 3.125, 0.4, and 0.05 µg/mL, respectively [2][3][4], and also displays potent cytotoxic effect on human lymphoblastic leukemia HL-60, KRAS mutation cell NCl-H358 and glioblastoma U251 and U87-MG cell lines with IC 50 values of 0.9, 0.15 0.475 and 1.77 µM, respectively [5][6][7][8][9]. Therefore, CA has the therapeutic potential for treatment of Gram-positive bacterial infections and cancers.…”

Section: Introductionmentioning

confidence: 99%

Optimization of fermentation conditions and medium components for chrysomycin A production by Streptomyces sp. 891-B6

Hu,

Weng,

Cai

et al. 2024

Preprint

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Background Chrysomycin A (CA) is a promising antibiotic for treatment of Gram-positive bacterial infections and cancers. In order to enhance CA yield, optimization of fermentation conditions and medium components was carried out on strain Streptomyces sp. 891-B6, an UV-induced mutant with improved CA titer compared with its wide-type marine strain 891. Results Using one-way experiment, the optimal fermentation conditions for CA production in 1-L shake flask were obtained as follows: 12 days of fermentation time, 5 days of seed age, 5% of inoculum volume ratio, 200 mL of loading volume and 6.5 of initial pH. By response surface methodology, the optimal medium components determined as glucose (39.239 g/L), corn starch (20.208 g/L), soybean meal (15.599 g/L) and CaCO3 (2.000 g/L). Conclusion Validation tests showed that the maximum yield of CA reached 1601.9 ± 56.7 mg/L, which was a 60% increase compared to the initial yield (952.3 ± 53.2 mg/L). These results provided an important basis for scale-up production of CA by strain 891-B6.

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“…Notably, they are lactone-bridged biaryls with potent antitumor activities, making them promising candidates for the development of new anticancer therapeutics and antibiotics [ 1 – 3 ]. The C -glycosylated natural product chrysomycin A ( 1 ), a member of the gilvocarcins [ 4 ], has shown significant promise in cancer therapy by functioning as a novel inhibitor of the topoisomerase II enzyme [ 5 ]. Another noteworthy example is the O -aryl glycosylated polyketide antibiotic chartreusin ( 2 ), first isolated in 1953 from Streptomyces chartreusis [ 6 ].…”

mentioning

confidence: 99%

Synthesis of C3-epi-virenose and anomerically activated derivatives

Röder,

Venegas,

Wurst

et al. 2024

Tetrahedron Letters

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Upgrade of chrysomycin A as a novel topoisomerase II inhibitor to curb KRAS-mutant lung adenocarcinoma progression

Cited by 6 publications

References 78 publications

Redefining bioactive small molecules from microbial metabolites as revolutionary anticancer agents

Redefining bioactive small molecules from microbial metabolites as revolutionary anticancer agents

Optimization of fermentation conditions and medium components for chrysomycin A production by Streptomyces sp. 891-B6

Synthesis of C3-epi-virenose and anomerically activated derivatives

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