각종 학술지 및 학회 논문 학계 소개

    국제 학술지 발표 (2013.01)-PLoS One January 11, 2013 8(1) e53900
    학술지  Komipharm 2014.03.18 10:21

KML001Displays Vascular Disrupting Properties and Irinotecan Combined Antitumor Activities in a Murine Tumor Model

Chang Hoon Moon, Seung Ju Lee, Ho Yong Lee, Jong CheolLee, HeeJeongCha, 
Wha JaCho, Jeong WooPark, Hyun Jin Park, Jin Seo, Young Han Lee, Ho-Taek Song, 
Young Joo Min


KML001 is sodium metaarsenite, and has shown cytotoxic activity in humantumor cell lines. The anti-cancer mechanism of KML001 involves 

cancer celldestruction due to DNA damage at the telomeres of cancer cell chromosomes. Inthis study, we assessed the vascular disrupting 

properties of KML001 andinvestigated whether KML001 as VDA is able to increase anti-tumor activity in irinotecan combined treatment.

We used a murine model of the CT26colon carcinoma cell line. CT26 isograftmice treated intraperitoneally with 10 mg/kg KML001displayed 

extensive central necrosis of tumor by 24 h. The vascular disruptingeffects of KML001 were assessed by dynamic contrast enhanced magnetic

resonanceimaging. Gadopentetic acid-diethylene triaminepentaacetic acid contrastenhancement was markedly decreased in KML001-treated 

mice one day aftertreatment, whereas persistently high signal enhancement was observed in miceinjected with saline. Rate constant Kep 

valuerepresenting capillary permeability was significantly decreased (p<0.05) inmice treated with KML001. Cytoskeletal changes of human 

umbilical vein endothelial cells (HUVECs)treated with 10 uM KML001 were assessedby immune blotting and confocal imaging. 

KML001degraded tubulin protein in HUVECs,which may be related to vascular disrupting properties of KML001. Finally, inthe mouse CT26 

isograft model, KML001combined with irinotecan significantlydelayed tumor growth as compared to control and irinotecan alone. These results 

suggest that KML001 is a novel vasculardisrupting agent, which exhibits significant vascular shut-down activity andenhances anti-tumor activity 

in combination with chemotherapy. These datafurther suggest an avenue for effective combination therapy in treating solidtumors.

'>Propidiumiodide (PI) staining also showed that NAC restored membrane integrity, damagedby sodium meta-arsenite.Therefore, these results 

suggestthat sodium meta-arsenite induces apoptotic, necrotic, and autophagiccell death through intracellular ROS accumulation in both 

androgen-sensitiveand androgen-insensitive prostate cancer cells and may be used as a newanticancer drug for the treatment of prostate cancer.