A novel compound NSC745885 exerts an anti-tumor effect on tongue cancer SAS cells in vitro and in vivo

PLoS One. 2014 Aug 15;9(8):e104703. doi: 10.1371/journal.pone.0104703. eCollection 2014.

Abstract

Objective: Oral squamous cell carcinoma (OSCC) is a prevalent cancer, especially in developing countries. Anthracyclines and their anthraquinone derivatives, such as doxorubicin, exhibit a cell growth inhibitory effect and have been used as anti-cancer drugs for many years. However, the cardiotoxicity of anthracycline antibiotics is a major concern in their clinical application. NSC745885 is a novel compound synthesized from 1,2-diaminoanthraquinone, which subsequently reacts with thionyl chloride and triethylamine. The present study aimed to investigate the anti-oral cancer potential and the safety of NSC745885.

Methods: We investigated the anti-cancer potential of NSC745885 in oral squamous carcinoma cell lines and in an in vivo oral cancer xenograft mouse model. The expression of apoptotic related genes were evaluated by real-time RT-PCR and western bloting, and the in vivo assessment of apoptotic marker were measured by immunohistochemical staining. The anti-tumor efficiency and safety between doxorubicin and NSC745885 were also compared.

Results: Our results demonstrated that NSC745885 exhibits anti-oral cancer activity through the induction of apoptosis in cancer cells and in tumor-bearing mice, and this treatment did not induce marked toxicity in experimental mice. This compound also exhibits a comparable anti-tumor efficiency and a higher safety in experimental mice when compared to doxorubicin.

Conclusions: The data of this study provide evidence for NSC745885 as a potential novel therapeutic drug for the treatment of human OSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthraquinones / adverse effects
  • Anthraquinones / chemistry
  • Anthraquinones / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects*
  • Carcinoma, Squamous Cell / drug therapy*
  • Caspase 3 / biosynthesis
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mouth Neoplasms / drug therapy*
  • Neoplasm Recurrence, Local / drug therapy
  • RNA, Messenger / biosynthesis
  • Thiadiazoles / adverse effects
  • Thiadiazoles / therapeutic use*
  • Tongue / pathology
  • Tongue Neoplasms / drug therapy*
  • X-Linked Inhibitor of Apoptosis Protein / biosynthesis
  • X-Linked Inhibitor of Apoptosis Protein / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Anthraquinones
  • Antineoplastic Agents
  • RNA, Messenger
  • Thiadiazoles
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • anthra(2,1-c)(1,2,5)thiadiazole-6,11-dione
  • Doxorubicin
  • Caspase 3
  • 1,2-diaminoanthraquinone

Grants and funding

This study was supported by research grants from the National Science Council, Taiwan, R.O.C. (NSC101-2320-B-016-016 to G.-J. Lin and NSC102-2314-B-016-018-MY3 to Y.-W. Chen), Tri-Service General Hospital, Republic of China (Grant No. TSGH-C102-019, TSGH-C100-034 and TSGH- C101-009-S06) and in part by the C.Y. Foundation for Advancement of Education, Science and Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.