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Isoniazid Could Be Used for Antibiotic-loaded Bone Cement for Musculoskeletal Tuberculosis: An In Vitro Study

Authors
 Chang Dong Han  ;  Taegwon Oh  ;  Sang-Nae Cho  ;  Jae Ho Yang  ;  Kwan Kyu Park 
Citation
 CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, Vol.471(7) : 2400-2406, 2013 
Journal Title
 CLINICAL ORTHOPAEDICS AND RELATED RESEARCH 
ISSN
 0009-921X 
Issue Date
2013
MeSH
Antibiotics, Antitubercular/administration & dosage ; Antibiotics, Antitubercular/chemistry ; Antibiotics, Antitubercular/pharmacology* ; Bone Cements/chemistry* ; Chemistry, Pharmaceutical ; Drug Carriers* ; Isoniazid/administration & dosage ; Isoniazid/chemistry ; Isoniazid/pharmacology* ; Microbial Sensitivity Tests ; Musculoskeletal Diseases/drug therapy* ; Mycobacterium tuberculosis/drug effects* ; Mycobacterium tuberculosis/growth & development ; Polymerization ; Rifampin/pharmacology ; Solubility ; Time Factors ; Tuberculosis/drug therapy* ; Tuberculosis, Osteoarticular/drug therapy*
Keywords
Tuberculosis ; Minimal Inhibitory Concentration ; Rifampicin ; Isoniazid ; Moxifloxacin
Abstract
Elevated KRAS expression has been frequently associated with cancer progression including breast cancer; however, therapeutic approaches targeting KRAS have been widely unsuccessful and KRAS mutant cancers remain unsolved problem in cancer therapy. In this study, we found that a new 2-pyrone derivative, 5-bromo-3-(3-hydroxyprop-1-ynyl)-2H-pyran-2-one (BHP) can block KRAS-driven breast cancer progression. Importantly, treatment with BHP effectively suppressed the migratory and invasive properties along with epithelial-mesenchymal transition (EMT) in MDA-MB231 breast cancer cells that carry oncogenic KRAS and mesenchymal malignant phenotypes. In parallel, BHP also sensitized the cells to anticancer treatment. Consistently, forced-expression of oncogenic KRAS bestowed the migratory and invasive properties, mesenchymal transition and resistance to anticancer treatment into normal human mammalian breast cells MCF10A and relatively non-malignant MCF7 and SK-BR3 breast cancer cells; however, treatment with BHP blocked those KRAS-induced malignant phenotypes. Notably, BHP interfered the interaction of KRAS with Raf-1 in concentration-dependent manner, thereby blocking the downstream effectors of KRAS signaling that is PI3K/AKT and ERK. Taken together, our findings indicate that the BHP, an α-pyrone derivative, suppresses malignant breast cancer progression by targeting of oncogenic KRAS signaling pathways.
Files in This Item:
T201301859.pdf Download
DOI
10.1007/s11999-013-2899-5
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Park, Kwan Kyu(박관규) ORCID logo https://orcid.org/0000-0003-0514-3257
Yang, Jae Ho(양재호) ORCID logo https://orcid.org/0000-0001-7421-2805
Oh, Tae Gwon(오태권)
Cho, Sang Nae(조상래)
Han, Chang Dong(한창동)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87062
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