• 한국미생물·생명공학회지
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• 제23권2호
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• pp.178-186
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• 1995

Streptomyces albus wild type ATCC 21838 produced salinomycin, polyether antibiotic. To clone genes related salinomycin production, a genomic library was screened using actI as a DNA hybridization probe. pWHM 210 was isolated, which contained an approximately 24 kb of insert DNA. A 3.8 kb region in the 24 kb insert DNA was hybridized to actI and the nucleotide sequence of this region was determinied. Two open reading frames found in the same direction were homologous to genes for $\beta$-keto acyl synthase/acyl transferase and chain length determining factor in type II PKS (polyketide synthase). The genes were components of minimal type II PKS genes, highly conserved and showed the strong simiarity to other type II PKS genes known today.

• Journal of Microbiology
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• 제45권1호
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• pp.6-10
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• 2007

Culture broth of a streptomycete isolate, Streptomyces sp. CS684 showed antibacterial activity on methicilin resistant Staphylococcus aureus (MRSA) and vancomycin resistant enterococci (VRE). Among purified substances from the organism, CSU-1, which is active against MRSA and VRE, is a $C_{37}H_{62}O_{12}Na\;(M^+,721.3875)$, and identified as laidlomycin. The anti-MRSA and anti-VRE activity of CSU-1 was stronger than oxacillin and vancomycin. Phylogenetic analysis showed that strain CS684 is very similar to Streptomyces ardus NRRL $2817^T$, whereas the ability of Streptomyces sp. CS684 to produce laidlomycin was shown to be unique.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.21-30
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• 2024

The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/β-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of β-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/β-catenin inhibition. Rescue studies using Wnt activator and β-catenin-overexpressing cells confirmed that β-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/β-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/β-catenin activation.

• 한국가금학회지
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• 제12권2호
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• pp.127-134
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• 1985

새로운 항콕시듐제인 polyether ionophorous antibiotics 인 Maduramicin ammonim 5 ppm 과 이미 수입되어 사용되고 있는 Salinomyc in 60ppm, 그리고 Monensin sodium 100 ppm등이 첨가된 사료로 초생추 240수를 사육하면서 이들 항콕시듐 효능 및 증체효과를 실험한 결과 다음과 같은 결과를 얻었다. 1. 육계의 증체량은 오오시스트의 인공접종 1주일 후에 Maduramicin 5ppm 투약구가 352.5g으로서 가장 높았고 무감염 무투약구가 332.5g, Salinomycin 60ppm 투약구가 329.8g, Monensin 100ppm, 투약구가 277.8g, 감염무투 약구가 226.0g 순으로 나타났다. 인공접종 2주일 후의 체중은 Maduramicin 투약구가 648.8g으로 가장 높았고, 무감염무투약구가 617.0g, Salinomycin 투약구가 614.8g, Monensin 투약구에서 579.5g, 감염무투약구가 529.3g 순으로 나타났다. 가장 안좋은 결과였다. 인공접종 2주일 후에도 Maduramicin 투약구가 1.680로 가장 우수하였고 감염투약구가 1.864로 가장 안 좋은 결과였다. 2. 사료효율은 인공접종 1주일 후에 Maduramicin 투약구에서 1.603fh 가장 우수하였고 감염투약구가 2.132로 가장 안 좋은 결과였다. 인공접종 2주일 후에도 Maduramicin 투약구가 1.680로 가장 우수하였고 감염무투약구가 1.864로 가장 안 좋은 결과였다. 3. 폐사율은 Maduramicin 투약구가 4.2%, Monensin 투약구가 8.3%, Salinomycin 투약구가 12.5%, 감염무투약구가 20.8%순으로 높게 나타났다. 4. 장의 병변도는 인공접종 1주일 후에 Monensin과 Maduramicin 투약구에서 각각 1.61과 1.72로 낮게 나타났고 감염무투약구에서는 2.92로 나타났다. 인공접종 2주일 후일에는 Maduramicin 투약구가 0.0425로 가장 낮게 나타났고 Salinomycin 투약구는 0.335, Monensin 투약구는 0.375로 높게 나타났다. 5. 오오시스트수는 인공접종 1주일째 Maduramicin 투약구가 가장 적게 배출되었고, 인공접종 2주후에도 1,400개로 상당히 낮게 배출되었으며 Monesin 투약구는 1, 2주째 모두 비교적 많은 수를 배출하였다. 6. 항콕시듐제의 효능을 평가하는 항콕시듐 지수는 인공접종 1주일 후에 무감염무투약구 200에 대하여 Maduramicin 투약구는 177.9, Salinomycin 투약구는 158.7, Monensin 투약구는 141.6, 감염무투약구는 78.0의 순서로 나타났다. 인공접종 2주일 후에는 무감염무투약구가 200에 대하여 Maduramicin 투약구가 201.1, Salinomycin 투약구가 184.0, Monensin 투약구가 182.4, 감염무투약구가 164.1의 순으로서 Maduramicin 투약구가 가장 우수하였다.

• Tuberculosis and Respiratory Diseases
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• 제75권1호
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• pp.9-17
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• 2013

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.