이영열
2018-02-13T05:18:49Z
2018-02-13T05:18:49Z
2016-03
INVESTIGATIONAL NEW DRUGS, v. 34, NO 1, Page. 1-14
0167-6997
1573-0646
https://link.springer.com/article/10.1007%2Fs10637-015-0301-z
http://hdl.handle.net/20.500.11754/37109
Arsenic compounds have been used in traditional medicine for several centuries. KML001 (sodium metaarsenite; NaAsO2) is an orally bio-available arsenic compound with potential anti-cancer activity. However, the effect of KML001 has not been studied in lymphoid neoplasms. The aim of this study is to evaluate the anti-proliferative effect of KML001 in non-Hodgkin's lymphoma and to compare its efficacy with As2O3. KML001 inhibited cellular proliferation in all tested lymphoma cell lines as well as JurkatR cells (adriamycin-resistant Jurkat cells) in a dose-dependent manner, while As2O3 was not effective. Cell cycle regulatory protein studies have suggested that KML001 induces G1 arrest via p27-induced inhibition of the kinase activities of CDK2, 4, and 6. Treatment of KML001 induced apoptosis in Jurkat and JurkatR cells. The apoptotic process was associated with down-regulation of Bcl-2 (antiapoptotic molecule), up-regulation of Bax (proapoptotic molecule), and inhibition of caspase-3, -8, and -9. In addition, cell signaling including the STAT, PI3K/Akt, MAPK, and NF-kappa B signal pathways were inhibited in KML001-treated Jurkat and JurkatR cells. Furthermore, targeting the telomere by KML001 was observed in the Jurkat and JurkatR cells. The In vivo anti-tumoral activity of KML001 was confirmed in a xenograft murine model. Interestingly, partial responses were seen in two lymphoma patients treated with 10 mg/day (follicular lymphoma for 16 weeks and mantle cell lymphoma for 24 weeks) without severe toxicities. These findings suggest that KML001 may be a candidate agent for the treatment of de novo, refractory, and relapsed non-Hodgkin's lymphoma patients.
The present study was conducted at Hanyang University Hospital Clinical Laboratory and Seoul National University College of Pharmacy, and this work was supported by Komipharm International Co., Ltd., Seoul, Korea.
en
SPRINGER
Non-Hodgkin's lymphoma
Sodium meta-arsenite
KML001
Cell signal
Telomere
Anti-tumoral effect of arsenic compound, sodium metaarsenite (KML001), in non-Hodgkin's lymphoma: an in vitro and in vivo study
Article
1
34
10.1007/s10637-015-0301-z
1-14
INVESTIGATIONAL NEW DRUGS
Yoon, Jin Sun
Hwang, Deok Won
Kim, Eun Shil
Kim, Jung Soon
Kim, Sujong
Chung, Hwa Jin
Lee, Sang Kook
Yi, Jun Ho
Uhm, Jieun
Lee, Young Yiul
2016003149
S
COLLEGE OF MEDICINE[S]
DEPARTMENT OF MEDICINE
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