Anti-leukemic effect of sodium metaarsenite (KML001) in acute myeloid leukemia with breaking-down the resistance of cytosine arabinoside

  • Authors:
    • Jin Sun Yoon
    • Eun Shil Kim
    • Byeong Bae Park
    • Jung Hye Choi
    • Young Woong Won
    • Sujong Kim
    • Young Yiul Lee
  • View Affiliations

  • Published online on: February 17, 2015     https://doi.org/10.3892/ijo.2015.2899
  • Pages: 1953-1962
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Sodium metaarsenite (NaAs2O3: code name KML001) is an orally bioavailable arsenic compound with potential anti-cancer activity. However, the effect of KML001 has not been studied in acute myeloid leukemia (AML). We investigated the anti-leukemic effect of KML001 in AML, and determined the mode of action of KML001. KML001 inhibited the cellular proliferation in all AML cell lines and primary AML blasts as well as HL-60R (cytosine arabinoside-resistant HL-60) cells, while As2O3 was not effective in primary AML blasts and AML cell lines including HL-60R cells. KML001 induced G1 arrest and apoptosis in HL-60 and HL-60R cells. KML001 inhibited the activation of STAT (signal transducer and activator of transcription) 1, 3, 5, NF-κB, AKT and PI3K, while phosphorylated PTEN was upregulated. In addition, activation of ERK, p38 and JNK was observed in KML001-induced growth inhibition of HL-60 and HL-60R cells. Furthermore, KML001 induced telomeric terminal restriction fragment (TRF) length shortening in a time-dependent manner in HL-60 and HL-60R cells. Real‑time PCR with RNA extracted from KML001-treated HL-60 and HL-60R cells showed a significant reduction of catalytic subunit of telomerase, hTERT, in a time-dependent manner. Additionally, γ-H2AX, a sensitive molecular marker of DNA damage, in HL-60 and HL-60R cells was induced by KML001. These results suggest that KML001 inhibits the proliferation of AML cells including cytosine arabinoside-resistant AML cells via various mechanisms such as cell cycle arrest, induction of apoptosis, inhibition of JAK/STAT and PI3K pathways, activation of MAPK pathway and telomere targeting.
View Figures
View References

Related Articles

Journal Cover

May-2015
Volume 46 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Yoon JS, Kim ES, Park BB, Choi JH, Won YW, Kim S and Lee YY: Anti-leukemic effect of sodium metaarsenite (KML001) in acute myeloid leukemia with breaking-down the resistance of cytosine arabinoside. Int J Oncol 46: 1953-1962, 2015
APA
Yoon, J.S., Kim, E.S., Park, B.B., Choi, J.H., Won, Y.W., Kim, S., & Lee, Y.Y. (2015). Anti-leukemic effect of sodium metaarsenite (KML001) in acute myeloid leukemia with breaking-down the resistance of cytosine arabinoside. International Journal of Oncology, 46, 1953-1962. https://doi.org/10.3892/ijo.2015.2899
MLA
Yoon, J. S., Kim, E. S., Park, B. B., Choi, J. H., Won, Y. W., Kim, S., Lee, Y. Y."Anti-leukemic effect of sodium metaarsenite (KML001) in acute myeloid leukemia with breaking-down the resistance of cytosine arabinoside". International Journal of Oncology 46.5 (2015): 1953-1962.
Chicago
Yoon, J. S., Kim, E. S., Park, B. B., Choi, J. H., Won, Y. W., Kim, S., Lee, Y. Y."Anti-leukemic effect of sodium metaarsenite (KML001) in acute myeloid leukemia with breaking-down the resistance of cytosine arabinoside". International Journal of Oncology 46, no. 5 (2015): 1953-1962. https://doi.org/10.3892/ijo.2015.2899