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

• Published in: PloS one Vol. 9; no. 8; p. e104703
• Main Authors: Chen, Yuan-Wu, Huang, Hsu-Shan, Shieh, Yi-Shing, Ma, Kuo-Hsing, Huang, Shing-Hwa, Hueng, Dueng-Yuan, Sytwu, Huey-Kang, Lin, Gu-Jiun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15-08-2014; Public Library of Science (PLoS)
• Subjects: Animals; Anthracycline; Anthraquinone; Anthraquinones - adverse effects; Anthraquinones - chemistry; Anthraquinones - therapeutic use; Antibiotics; Anticancer properties; Antineoplastic Agents - therapeutic use; Apoptosis; Apoptosis - drug effects; Biocompatibility; Biology; Cancer; Cancer therapies; Carcinoma, Squamous Cell - drug therapy; Cardiomyopathy; Cardiotoxicity; Caspase 3 - biosynthesis; Caspase 3 - genetics; Caspase 3 - metabolism; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Chemotherapy; Cytotoxicity; Data processing; Dentistry; Developing countries; DNA damage; Doxorubicin; Doxorubicin - adverse effects; Doxorubicin - therapeutic use; Gene expression; Humans; LDCs; Medicine and Health Sciences; Mice; Mice, Inbred NOD; Mice, SCID; Mouth Neoplasms - drug therapy; Neoplasm Recurrence, Local - drug therapy; Oral cancer; Oral squamous cell carcinoma; Polymerase chain reaction; RNA, Messenger - biosynthesis; Safety; Squamous cell carcinoma; Studies; Surgery; Telomerase; Thiadiazoles - adverse effects; Thiadiazoles - therapeutic use; Tongue; Tongue - pathology; Tongue Neoplasms - drug therapy; Toxicity; Triethylamine; Tumor cell lines; Tumors; X-Linked Inhibitor of Apoptosis Protein - biosynthesis; X-Linked Inhibitor of Apoptosis Protein - genetics; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation; China; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104703

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