Antitumoral effect of arsenic compound, sodium metaarsenite (KML001), on multiple myeloma cells

Seo Ju Kim, Eun Shil Kim, Sujong Kim, Jieun Uhm, Young Woong Won, Byeong Bae Park, Jung Hye Choi, Young Yiul Lee

Research output: Contribution to journalArticle

Abstract

KML001 (sodium metaarsenite;NaAs2O3) is known to have antitumor activity against a variety of cancers. In this study, we examined its effect on multiple myeloma (MM). KML001 reduced the growth of all MM cell lines examined with an IC50 of 5x10-8 M. Exposure to KML001 (5x10-8 M) decreased levels of cyclins A/B1/D1/E1, CDK2/4/6 in U266 cells and increased the p21 and p27 levels. Furthermore, p21 became bound to CDK2/4/6, resulting in a reduction of CDK2/4/6 kinase activity. The cleaved forms of Bcl-2, and caspases-3,-8 and-9 were detected, and the anti-Apoptotic molecule, Bax, also increased. Activation of STAT1/3, NF-κB (p65 and p50 subunits), pAKT and pERK decreased, and p-PTEN increased. There was also a significant reduction of hTERT at 12 h and upregulation of γ-H2AX and CHK1/2 molecules at 24 h. Thus, KML001 appears to have antitumor activity against MM by inhibiting various oncogenic signaling pathways. It may be useful for treating MM.

Original languageEnglish
Pages (from-to)1739-1746
Number of pages8
JournalInternational Journal of Oncology
Volume51
Issue number6
DOIs
StatePublished - 2017 Dec

Fingerprint

Arsenicals
Multiple Myeloma
Cyclin B1
Cyclin A
Caspase 8
Caspase 3
Inhibitory Concentration 50
Phosphotransferases
Up-Regulation
sodium arsenite
Cell Line
Growth
Neoplasms

Keywords

  • Cell cycle
  • Cell signaling
  • KML001
  • Multiple myeloma
  • Telomere

Cite this

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title = "Antitumoral effect of arsenic compound, sodium metaarsenite (KML001), on multiple myeloma cells",
abstract = "KML001 (sodium metaarsenite;NaAs2O3) is known to have antitumor activity against a variety of cancers. In this study, we examined its effect on multiple myeloma (MM). KML001 reduced the growth of all MM cell lines examined with an IC50 of 5x10-8 M. Exposure to KML001 (5x10-8 M) decreased levels of cyclins A/B1/D1/E1, CDK2/4/6 in U266 cells and increased the p21 and p27 levels. Furthermore, p21 became bound to CDK2/4/6, resulting in a reduction of CDK2/4/6 kinase activity. The cleaved forms of Bcl-2, and caspases-3,-8 and-9 were detected, and the anti-Apoptotic molecule, Bax, also increased. Activation of STAT1/3, NF-κB (p65 and p50 subunits), pAKT and pERK decreased, and p-PTEN increased. There was also a significant reduction of hTERT at 12 h and upregulation of γ-H2AX and CHK1/2 molecules at 24 h. Thus, KML001 appears to have antitumor activity against MM by inhibiting various oncogenic signaling pathways. It may be useful for treating MM.",
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Antitumoral effect of arsenic compound, sodium metaarsenite (KML001), on multiple myeloma cells. / Kim, Seo Ju; Kim, Eun Shil; Kim, Sujong; Uhm, Jieun; Won, Young Woong; Park, Byeong Bae; Choi, Jung Hye; Lee, Young Yiul.

In: International Journal of Oncology, Vol. 51, No. 6, 12.2017, p. 1739-1746.

Research output: Contribution to journalArticle

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AU - Kim, Seo Ju

AU - Kim, Eun Shil

AU - Kim, Sujong

AU - Uhm, Jieun

AU - Won, Young Woong

AU - Park, Byeong Bae

AU - Choi, Jung Hye

AU - Lee, Young Yiul

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AB - KML001 (sodium metaarsenite;NaAs2O3) is known to have antitumor activity against a variety of cancers. In this study, we examined its effect on multiple myeloma (MM). KML001 reduced the growth of all MM cell lines examined with an IC50 of 5x10-8 M. Exposure to KML001 (5x10-8 M) decreased levels of cyclins A/B1/D1/E1, CDK2/4/6 in U266 cells and increased the p21 and p27 levels. Furthermore, p21 became bound to CDK2/4/6, resulting in a reduction of CDK2/4/6 kinase activity. The cleaved forms of Bcl-2, and caspases-3,-8 and-9 were detected, and the anti-Apoptotic molecule, Bax, also increased. Activation of STAT1/3, NF-κB (p65 and p50 subunits), pAKT and pERK decreased, and p-PTEN increased. There was also a significant reduction of hTERT at 12 h and upregulation of γ-H2AX and CHK1/2 molecules at 24 h. Thus, KML001 appears to have antitumor activity against MM by inhibiting various oncogenic signaling pathways. It may be useful for treating MM.

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