Investigational New Drugs

, Volume 28, Issue 3, pp 205–215

Augmented antitumor effects of combination therapy of cisplatin with ethaselen as a novel thioredoxin reductase inhibitor on human A549 cell in vivo

PRECLINICAL STUDIES

DOI: 10.1007/s10637-009-9235-7

Cite this article as:
Tan, Q., Li, J., Yin, H. et al. Invest New Drugs (2010) 28: 205. doi:10.1007/s10637-009-9235-7

Summary

Ethaselen (1, 2-[bis (1, 2-Benzisoselenazolone-3 (2H) -ketone)] ethane, BBSKE), as a novel organoselenium compound targeting thioredoxin reductase (TrxR), has been reported to inhibit tumor growth and TrxR activity in several human tumor cell lines. It has now entered Phase I clinical trails. Here we report the effects of ethaselen and cisplatin (cis-diamminedichloroplatinum II, DDP) combination therapy (ethaselen 36 mg/kg, i.g., o.d. × 10 d and cisplatin 1 mg/kg, i.p., single at day 0) on human A549-grafted nude mouse model (female, BALB/c nude mouse, n = 5, treatment after tumor volume reached 100 mm3). Compared to single drug administration (either ethaselen: 36 mg/kg, i.g., o.d. × 10 d or cisplatin: 1.0 mg/kg, i.p., single at day 0), the combination therapy showed significantly reduced tumor size (presumably due to a synergistic effect) and no obvious toxic damage (both in terms of body weight maintenance and liver/kidney damage). These results will be significant in the development of novel anti-tumoral therapeutic strategies directed to non-small cell lung cancer (NSCLC).

Keywords

EthaselenThioredoxin reductase inhibitorCisplatinNon-small cell lung cancerCombination chemotherapySynergistic effect

Abbreviations

Ethaselen (BBSKE)

1, 2-[bis (1,2-Benzisoselenazolone-3 (2H) -ketone)]ethane

BUN

Blood urea nitrogen

Cre

Creatinine

HE

Hematoxylin eosin

GSH

Glutathione

GSH-Px

Glutathione-peroxidase

MDA

Malondialdehyde

NOAEL

No-observed adverse effect level

NSCLC

Non-small cell lung cancer

SPF

Specific pathogen free

TMP

1,1,3,3-Tetramethoxypropane

TrxR

Thioredoxin reductase

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Qiang Tan
    • 1
    • 2
  • Jing Li
    • 1
  • Han-wei Yin
    • 3
  • Li-hui Wang
    • 1
  • Wan-chen Tang
    • 1
  • Fang Zhao
    • 1
  • Xin-min Liu
    • 2
  • Hui-hui Zeng
    • 1
    • 4
  1. 1.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical SciencesPeking UniversityBeijingChina
  2. 2.Peking University First HospitalBeijingChina
  3. 3.College of Life SciencesPeking UniversityBeijingChina
  4. 4.School of Pharmaceutical SciencesPeking University Health Science CenterBeijingChina