DMNQ S-53 induces apoptosis and inhibits the growth of Lewis lung carcinoma cells in vitro and in vivo

Jae Ho Lee, Eun Ok Lee, Hyo Jung Lee, Kwan Hyun Kim, Kyoo Seok Ahn, Sung-Joon Lee, Ji Young Kim, Sung Hoon Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: 6-(1-Proproxyiminomethyl)-5,8-dimethoxy-1,4-naphthoquinone S-53 (DMNQ S-53) was synthesized to develop a novel anti-tumor agent against lung cancer. Methods: Cytotoxicity assay, DNA fragmentation assay, cell cycle analysis, mitochondrial potential measurement and Western blotting were employed in vitro and also Lewis lung carcinoma (LLC) animal model was used for evaluating the anti-tumor of DMNQ S53 in vivo. Results and conclusions: DMNQ S-53 exerted cytotoxicity against LLC cells with IC50 of ∼5 μM. DMNQ S-53 also increased the sub G1 cell population stained by propidium iodide (PI) as well as ladder-like DNA fragmentation in a concentration dependent manner. Western blot analysis revealed that DMNQ S-53 induced apoptosis was associated with the activation of caspase-9 and -3, cleavage of poly (ADP-ribose) polymerase (PARP) and the increased ratio of Bax to Bcl-2 expression in LLC cells in a concentration dependent manner. In addition, DMNQ S-53 reduced mitochondrial potential suggesting the involvement of the mitochondrial intrinsic pathway. Furthermore, intraperitoneally injection of DMNQ S-53 resulted in the inhibition of the tumor volume/weight of LLC cells inoculated on the flank of C57BL6 mice up to ∼50%. Taken together, these results strongly indicate that DMNQ S-53 may inhibit LLC tumor growth in vitro and in vivo via apoptosis induction through the mitochondria-mediated caspase activation pathway.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalJournal of Cardiothoracic-Renal Research
Volume1
Issue number1
DOIs
Publication statusPublished - 2006 Mar 1

Keywords

  • Apoptosis
  • DMNQ S-53
  • DNA fragmentation
  • LLC cells
  • Mitochondrial pathway

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Nephrology
  • Pulmonary and Respiratory Medicine

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