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

Title
Isoniazid Could Be Used for Antibiotic-loaded Bone Cement for Musculoskeletal Tuberculosis: An In Vitro Study
Authors
Chang Dong Han;Taegwon Oh;Kwan Kyu Park;Jae Ho Yang;Sang-Nae Cho
Issue Date
2013
Journal Title
Clinical Orthopaedics and Related Research
ISSN
0009-921X
Citation
Clinical Orthopaedics and Related Research, Vol.471(7) : 2400~2406, 2013
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.
URI
http://www.sciencedirect.com/science/article/pii/S0304383513004059

http://ir.ymlib.yonsei.ac.kr/handle/22282913/87062
DOI
10.1016/j.canlet.2013.05.023
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Microbiology
1. 연구논문 > 1. College of Medicine > Dept. of Orthopedic Surgery
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
Yonsei Authors
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