School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Biochem Pharmacol. 2020 Jan;171:113713. doi: 10.1016/j.bcp.2019.113713. Epub 2019 Nov 14.
Oral cancer is a prevalent cancer in male worldwide. Oral potentially malignant disorders (OMPDs) are the oral mucosa lesions that have high malignant transformation rate to oral cancer. The mainstay for OMPDs treatment includes carbon dioxide (CO) laser and surgery, which may lead to the side effects of scarring and impaired function of oral cavity in the patients and reduced their willingness to receive curative therapy. Therefore, developing a non-invasive and function-preserving therapy is clinically important. Since development of a novel chemotherapeutic drug requires a lot of time and cost, we applied the high-throughput screening (HTS) approach to identify new bioactivities for FDA-approved drugs, known as drug repurposing. Through this drug repurposing approach, we discovered that gentian violet (GV), which is well known for its antibacterial, antifungal, antihelminthic, antitrypanosomal and antiviral activities, was able to induce significant cell death in DOK oral precancerous cells through ROS production. Moreover, decreased phosphorylation of p53(Ser15) and NFκB(Ser536) was required for GV-induced cell death. In vivo, 3% GV orabase effectively suppressed the progression of DMBA-induced oral precancerous lesions. In conclusion, this new formulation of GV through drug repurposing has the potential to be further developed as a therapeutic drug for OPMD clinically.
口腔癌是全球男性中常见的癌症。口腔潜在恶性疾病（OMPD）是具有高恶性转化为口腔癌的口腔黏膜病变。OMPD 的主要治疗方法包括二氧化碳（CO）激光和手术，这可能会导致患者出现疤痕和口腔功能受损等副作用，并降低他们接受治疗的意愿。因此，开发一种非侵入性和保留功能的治疗方法具有重要的临床意义。由于开发一种新型化疗药物需要大量的时间和成本，我们应用高通量筛选（HTS）方法来识别已获 FDA 批准的药物的新生物活性，这被称为药物再利用。通过这种药物再利用的方法，我们发现龙胆紫（GV），它以其抗菌、抗真菌、抗寄生虫、抗锥虫和抗病毒活性而闻名，能够通过产生 ROS 诱导 DOK 口腔癌前细胞发生显著的细胞死亡。此外，GV 诱导的细胞死亡需要降低 p53（Ser15）和 NFκB（Ser536）的磷酸化。在体内，3%龙胆紫口腔糊剂能够有效抑制 DMBA 诱导的口腔癌前病变的进展。总之，通过药物再利用开发的这种新形式的 GV 有可能进一步开发为 OPMD 的临床治疗药物。
