Structures and biological activities of novel 4’-acetylated analogs of chrysomycins A and B

Wada, Shun‐ichi; Sawa, Ryûichi; Iwanami, Fumiki; Nagayoshi, Miho; Kubota, Yumiko; Iijima, Kiyoko; Hayashi, Chikara; Shibuya, Yuko; Hatano, Masaki; Igarashi, Masayuki; Kawada, Manabu

doi:10.1038/ja.2017.99

Cited by 16 publications

(13 citation statements)

References 15 publications

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“…In 1955, chrysomycin was first discovered from an unknown Streptomyces described as slender greenish-yellow needles or crystallized rods [ 5 ]. Chrysomycin A (Chr-A) ( Figure 1 , C28H28O9 and MW508.52), the major component, differs from chrysomycin B, the second component with the vinyl group of the 8-position [ 5 ], thus showing cytotoxicity towards cancer cells [ 6 , 7 ]. These years, conditions and preparation of Chr-A production has been greatly optimized, which is of great significance to its new drug development process [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Chrysomycin A Inhibits the Proliferation, Migration and Invasion of U251 and U87-MG Glioblastoma Cells to Exert Its Anti-Cancer Effects

Liu

Zhang

et al. 2022

Molecules

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Chrysomycin A (Chr-A), an antibiotic from Streptomyces, is reported to have anti-tumor and anti-tuberculous activities, but its anti-glioblastoma activity and possible mechanism are not clear. Therefore, the current study was to investigate the mechanism of Chr-A against glioblastoma using U251 and U87-MG human cells. CCK8 assays, EdU-DNA synthesis assays and LDH assays were carried out to detect cell viability, proliferation and cytotoxicity of U251 and U87-MG cells, respectively. Transwell assays were performed to detect the invasion and migration abilities of glioblastoma cells. Western blot was used to validate the potential proteins. Chr-A treatment significantly inhibited the growth of glioblastoma cells and weakened the ability of cell migration and invasion by down regulating the expression of slug, MMP2 and MMP9. Furthermore, Chr-A also down regulated Akt, p-Akt, GSK-3β, p-GSK-3β and their downstream proteins, such as β-catenin and c-Myc in human glioblastoma cells. In conclusion, Chr-A may inhibit the proliferation, migration and invasion of glioblastoma cells through the Akt/GSK-3β/β-catenin signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Chrysomycin A Inhibits the Proliferation, Migration and Invasion of U251 and U87-MG Glioblastoma Cells to Exert Its Anti-Cancer Effects

Liu

Zhang

et al. 2022

Molecules

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“…1 ) is the major analogue of chrysomycins and plays the most potent role in this complex [ 2 ]. Compared with the clinically used anticancer agent doxorubicin, CA shows significant cytotoxicity toward cancer cells because of its vinyl group in the 8-position [ 3 , 4 ]. In addition to strong antineoplastic and antibacterial properties of CA [ 5 – 7 ], it is thought to act as an inhibitor of the catalytic activity of human topoisomerase II [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanochemical preparation of chrysomycin A self-micelle solid dispersion with improved solubility and enhanced oral bioavailability

Zheng

Gao

et al. 2021

J Nanobiotechnol

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Background Chrysomycin A (CA) has been reported as numerous excellent biological activities, such as antineoplastic and antibacterial. Though, poor solubility of CA limited its application in medical field. Due to good amphiphilicity and potential anticancer effect of disodium glycyrrhizin (Na2GA) as an excipient, an amorphous solid dispersion (Na2GA/CA-BM) consisting of CA and Na2GA was prepared in the present study by mechanochemical technology (roll mill ML-007, zirconium balls, 30 rpm, 2.5 h) to improve the solubility and oral bioavailability of CA. Then, Na2GA/CA-BM was self-assembled to micelles in water. The interaction of CA and Na2GA in solid state were investigated by X-ray diffraction studies, polarized light microscopy, and scanning electron microscope. Meanwhile, the properties of the sample solution were analyzed by dynamic light scattering and transmission electron. Furthermore, the oral bioavailability and antitumor ability of Na2GA/CA-BM in vivo were tested, providing a theoretical basis for future application of CA on cancer therapy. Results CA encapsulated by Na2GA was self-assembled to nano-micelles in water. The average diameter of nano-micelle was 131.6 nm, and zeta potential was − 11.7 mV. Three physicochemical detections showed that CA was transformed from crystal into amorphous form after treated with ball milling and the solubility increased by 50 times. Na2GA/CA-BM showed a significant increase of the bioavailability about two time that of free CA. Compared with free CA, the in-vivo antitumor studies also exhibited that Na2GA/CA-BM had an excellent inhibition of tumor growth. Conclusions Na2GA/CA-BM nanoparticles (131.6 nm, − 11.7 mV) prepared by simple and low-cost mechanochemical technology can improve oral bioavailability and antitumor efficacy of CA in vivo, suggesting a potential formulation for efficient anticancer treatment. Graphic abstract

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“…Chrysomycin A (Chr-A, Fig. 1A), a kind of glycoside with benzonaphthopyranone, was first discovered in 1955 [7,8]. In recent years, progress has been made in production conditions and preparation of Chr-A, which has contributed to its future new drug development process [9,10].…”

Section: Introductionmentioning

confidence: 99%

Chrysomycin a Regulates Proliferation and Apoptosis of Neuroglioma Cells via Akt/GSK-3β Signaling Pathway In Vivo and In Vitro

Liu¹,

Liu²,

Shang³

et al. 2023

Preprint

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Glioblastoma (GBM) is a major type of primary brain tumors without ideal prognosis and it’s necessary to find novel compound possessing therapeutic effect. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates apoptosis of neuroglioma cells is unclear.The present study was to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates apoptosis of neuroglioma cells. Briefly, The an-ti-glioblastoma activity was assessed in human glioma U87 xenografts nude mice. Chr-A-related targets were identified by RNA-seq. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed by flow cytometry. Apoptosis-related proteins and possible molecular mecha-nism were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografts nude mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathway were involved in the possible mechanism. Chr-A increased apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blot revealed that Chr-A broke the balance between Bax and Bcl-2 activating caspase cascade re-action and downregulated the expression of p-Akt and p-GSK-3β, suggesting that Chr-A may contribute to glioblastoma regression modulating Akt/GSK-3β signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.

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Structures and biological activities of novel 4’-acetylated analogs of chrysomycins A and B

Cited by 16 publications

References 15 publications

Chrysomycin A Inhibits the Proliferation, Migration and Invasion of U251 and U87-MG Glioblastoma Cells to Exert Its Anti-Cancer Effects

Chrysomycin A Inhibits the Proliferation, Migration and Invasion of U251 and U87-MG Glioblastoma Cells to Exert Its Anti-Cancer Effects

Mechanochemical preparation of chrysomycin A self-micelle solid dispersion with improved solubility and enhanced oral bioavailability

Chrysomycin a Regulates Proliferation and Apoptosis of Neuroglioma Cells via Akt/GSK-3β Signaling Pathway In Vivo and In Vitro

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